Publication: Velcrin molecular glues induce apoptosis in glioblastomas with high PDE3A and SLFN12 expression
Velcrins are a novel class of molecular glues that induce formation of a protein complex between the RNase SLFN12 and the phosphodiesterase PDE3A. This complex was found to activate RNase activity of SLFN12 and lead to selective cleavage of tRNALeu(TAA), thus halting translation and causing apoptosis. This study investigated the activity of velcrins as anti-cancer agents in glioblastomas. Velcrins were found to halt the growth of glioblastoma cell lines and patient-derived models with high PDE3A and SLFN12 expression. The velcrin BAY 2666605 was found to be a central nervous-system-penetrant compound that causes tumor regression in an orthotopic xenograft model of glioblastoma. In summary, our study suggests that velcrins may have promising therapeutic potential in a subset of glioblastomas.
Velcrins are a novel class of molecular glues that induce formation of a protein complex between the RNase SLFN12 and the phosphodiesterase PDE3A. This complex was found to activate RNase activity of SLFN12 and lead to selective cleavage of tRNALeu(TAA), thus halting translation and causing apoptosis. This study investigated the activity of velcrins as anti-cancer agents in glioblastomas. Velcrins were found to halt the growth of glioblastoma cell lines and patient-derived models with high PDE3A and SLFN12 expression. The velcrin BAY 2666605 was found to be a central nervous-system-penetrant compound that causes tumor regression in an orthotopic xenograft model of glioblastoma. In summary, our study suggests that velcrins may have promising therapeutic potential in a subset of glioblastomas.
Publication: An essential role for Cmtr2 in mammalian embryonic development
In the current work, Alena Yermalovich and colleagues have investigated the normal physiological function of a novel tumor suppressor gene, CMTR2 (also known as FTSJD1). Genomic analysis of lung adenocarcinomas by our group has revealed statistically significant somatic loss-of-function mutations in CMTR2 (Campbell et al., 2016). CMTR2 is an mRNA cap methyltransferase with poorly understood physiological functions. We found that this lung cancer tumor suppressor gene plays a critical role in endothelial cell function and vascular development. This work provides the groundwork to understand the role of this tumor suppressor protein in normal physiology and should be the basis for many future studies elucidating pathways in both carcinogenesis and vascular development.
In the current work, Alena Yermalovich and colleagues have investigated the normal physiological function of a novel tumor suppressor gene, CMTR2 (also known as FTSJD1). Genomic analysis of lung adenocarcinomas by our group has revealed statistically significant somatic loss-of-function mutations in CMTR2 (Campbell et al., 2016). CMTR2 is an mRNA cap methyltransferase with poorly understood physiological functions. We found that this lung cancer tumor suppressor gene plays a critical role in endothelial cell function and vascular development. This work provides the groundwork to understand the role of this tumor suppressor protein in normal physiology and should be the basis for many future studies elucidating pathways in both carcinogenesis and vascular development.
Lab Member Farewell and Congratulations 2024
Ananya Kodali and Akansha Gupta have been associate computational biologists working with Andy Cherniack. Ananya Kodali has continued to study medicine at the NYU Grossman School of Medicine. Akansha Gupta is now pursuing a PhD at the University of Chicago.
Sawyer Anderson has been a research associate working with Kristy to understand the mechanisms of novel cancer therapeutics that target tumor cells expressing high levels of SLFN12. He is now studying biochemistry as a part of the PhD program at University of North Carolina at Chapel Hill.
Will Gibson has been a postdoctoral scientist with the Meyerson lab since 2020. He is now working on inventing novel chemical biology technologies to address some of cancer's most intractable problems, such as directly drugging TP53 mutant cancers, in his new lab at Dana Farber Cancer Institute.
We wish them all best and look forward to hearing about their future endeavors!
Ananya Kodali and Akansha Gupta have been associate computational biologists working with Andy Cherniack. Ananya Kodali has continued to study medicine at the NYU Grossman School of Medicine. Akansha Gupta is now pursuing a PhD at the University of Chicago.
Sawyer Anderson has been a research associate working with Kristy to understand the mechanisms of novel cancer therapeutics that target tumor cells expressing high levels of SLFN12. He is now studying biochemistry as a part of the PhD program at University of North Carolina at Chapel Hill.
Will Gibson has been a postdoctoral scientist with the Meyerson lab since 2020. He is now working on inventing novel chemical biology technologies to address some of cancer's most intractable problems, such as directly drugging TP53 mutant cancers, in his new lab at Dana Farber Cancer Institute.
We wish them all best and look forward to hearing about their future endeavors!
Publication: Neotelomeres and telomere-spanning chromosomal arm fusions in cancer revealed by long-read sequencing
In tumor genomes, telomeres can be found outside their normal locations at the ends of chromosomes. The origins and structures of these "neotelomeres" are unclear, as analysis of repetitive genomic elements like these using short-read sequencing has been challenging. To explore telomere structures in cancer cell lines and samples, Kar-Tong Tan, Heng Li, Matthew Meyerson, and colleagues used long-read sequencing to identify neotelomeres, as well as events where short telomeres fuse with chromosomal arms and other complex telomeric alterations. Additionally, using short-read sequencing they saw that these events vary in frequency across 40 cancer types. Their framework can help examine other highly repetitive sequences such as centromere arrays.
Read the paper here
In tumor genomes, telomeres can be found outside their normal locations at the ends of chromosomes. The origins and structures of these "neotelomeres" are unclear, as analysis of repetitive genomic elements like these using short-read sequencing has been challenging. To explore telomere structures in cancer cell lines and samples, Kar-Tong Tan, Heng Li, Matthew Meyerson, and colleagues used long-read sequencing to identify neotelomeres, as well as events where short telomeres fuse with chromosomal arms and other complex telomeric alterations. Additionally, using short-read sequencing they saw that these events vary in frequency across 40 cancer types. Their framework can help examine other highly repetitive sequences such as centromere arrays.
Read the paper here
Congratulations to John Pulice on completion of his thesis -- April 2024
Congratulations to Dr. John Pulice, who successfully defended his thesis, Dosage amplification dictates oncogenic regulation by the NKX2-1 lineage factor in lung adenocarcinoma, on April 22. John Pulice graduates from the Biological and Biomedical Sciences (BBS) Program of Harvard University.
Congratulations to Dr. John Pulice, who successfully defended his thesis, Dosage amplification dictates oncogenic regulation by the NKX2-1 lineage factor in lung adenocarcinoma, on April 22. John Pulice graduates from the Biological and Biomedical Sciences (BBS) Program of Harvard University.
Publication: Comprehensive mutational scanning of EGFR reveals TKI sensitivities of extracellular domain mutants
Tiki Hayes and colleagues published a paper in Nature Communications describing results from their deep mutational scanning of EGFR, which was followed by a high-throughput functional genetic screen and analysis of patient data, where they identified variants with differing sensitivities to a range of EGFR TKIs. Read the paper here
Tiki Hayes and colleagues published a paper in Nature Communications describing results from their deep mutational scanning of EGFR, which was followed by a high-throughput functional genetic screen and analysis of patient data, where they identified variants with differing sensitivities to a range of EGFR TKIs. Read the paper here
Breakthrough Therapy Designation for BAY2927088
The Food and Drug Administration (FDA) has granted “Breakthrough Therapy” designation for BAY2927088, an investigational phase compound developed as part of our collaboration with Bayer. This compound is now undergoing clinical trials for the treatment of NSCLC with somatic ERBB2 mutations. The project has developed out of a long-standing effort by Heidi Greulich on exon 20 insertion mutants of EGFR, going back to her original paper demonstrating these mutants to be resistant to conventional EGFR inhibitors (link to Greulich et al., PLoS Med, 2005). Read about it here!!!
The Food and Drug Administration (FDA) has granted “Breakthrough Therapy” designation for BAY2927088, an investigational phase compound developed as part of our collaboration with Bayer. This compound is now undergoing clinical trials for the treatment of NSCLC with somatic ERBB2 mutations. The project has developed out of a long-standing effort by Heidi Greulich on exon 20 insertion mutants of EGFR, going back to her original paper demonstrating these mutants to be resistant to conventional EGFR inhibitors (link to Greulich et al., PLoS Med, 2005). Read about it here!!!
Publication: XRN1 deletion induces PKR-dependent cell lethality in interferon-activated cancer cells
Recent studies have shown that activation of innate immune sensors of double-stranded RNA (dsRNA) may represent an effective strategy to kill cancer cells. In a follow-up study to our work on ADAR1 genetic dependency, we now show that depletion of the exoribonuclease XRN1 causes lethality in cancer cells with activation of the interferon response pathway. These interferon-activated cancer cells have high levels of the interferon-inducible dsRNA sensor protein kinase R (PKR), predisposing them to XRN1 loss. Inhibition of interferon receptor signaling causes decreased PKR levels and rescues cell viability after XRN1 inactivation in cancer cells with baseline interferon pathway activation. Conversely, stimulation of interferon signaling in cancer cells with low interferon pathway activity can induce vulnerability to XRN1 loss in a PKR-dependent manner. Finally, we find that depletion of XRN1 causes accumulation of complementary sense and antisense transcript pairs, which represent putative PKR ligands. Together, these data show how XRN1 regulates the dsRNA sensor PKR and nominate XRN1 as a potential therapeutic target in cancers with an activated interferon cell state. Read the paper here
Recent studies have shown that activation of innate immune sensors of double-stranded RNA (dsRNA) may represent an effective strategy to kill cancer cells. In a follow-up study to our work on ADAR1 genetic dependency, we now show that depletion of the exoribonuclease XRN1 causes lethality in cancer cells with activation of the interferon response pathway. These interferon-activated cancer cells have high levels of the interferon-inducible dsRNA sensor protein kinase R (PKR), predisposing them to XRN1 loss. Inhibition of interferon receptor signaling causes decreased PKR levels and rescues cell viability after XRN1 inactivation in cancer cells with baseline interferon pathway activation. Conversely, stimulation of interferon signaling in cancer cells with low interferon pathway activity can induce vulnerability to XRN1 loss in a PKR-dependent manner. Finally, we find that depletion of XRN1 causes accumulation of complementary sense and antisense transcript pairs, which represent putative PKR ligands. Together, these data show how XRN1 regulates the dsRNA sensor PKR and nominate XRN1 as a potential therapeutic target in cancers with an activated interferon cell state. Read the paper here
Farewell and Congratulations Kar-Tong Tan and Doug Wheeler
Kar-Tong Tan has been a graduate student and postdoctoral scientist with the Meyerson Lab since 2018 working on delineating neotelemeres in lung adenocarcinoma using both long and short read sequencing. He has now joined the University of Singapore as an Assistant Professor of Department of Pharmacy and Pharmaceutical Sciences, and Department of Biomedical Informatics.
Doug Wheeler has been a postdoctoral scientist with the Meyerson lab since 2015 working on identifying and characterizing second messengers using liquid chromatography–mass spectrometry. He has now continued to join a start-up institution...to be announced!
We wish them both best and look forward to hearing about their future endeavors!
Kar-Tong Tan has been a graduate student and postdoctoral scientist with the Meyerson Lab since 2018 working on delineating neotelemeres in lung adenocarcinoma using both long and short read sequencing. He has now joined the University of Singapore as an Assistant Professor of Department of Pharmacy and Pharmaceutical Sciences, and Department of Biomedical Informatics.
Doug Wheeler has been a postdoctoral scientist with the Meyerson lab since 2015 working on identifying and characterizing second messengers using liquid chromatography–mass spectrometry. He has now continued to join a start-up institution...to be announced!
We wish them both best and look forward to hearing about their future endeavors!
Publication: Bifunctional Small Molecules That Induce Nuclear Localization and Targeted Transcriptional Regulation
In recent years, chemical induced proximity has been used to induce various post-translational modifications to target proteins such as ubiquitination for targeted protein degradation, or phosphorylation and dephosphorylation. In this study, William Gibson and Ananthan Sadagopan describe a novel modality within induced proximity therapeutics: Targeted Protein Relocalization. They developed small molecules that leverage the nuclear-localized protein BRD4 to transport cytosolic proteins into the nucleus. In one example, they showed the nuclear relocalization of mutant NPM1c, a protein that is mislocalized into the cytosol due to genetic mutations in AML. They also showed that these small molecules can be used to increase transcription of DNA binding proteins due to recruitment of the transcriptional machinery. These findings pave the way for the rewiring and restoration of cellular processes through induced proximity, with significant implications for disease therapy in cancer and other areas. Read the paper here
In recent years, chemical induced proximity has been used to induce various post-translational modifications to target proteins such as ubiquitination for targeted protein degradation, or phosphorylation and dephosphorylation. In this study, William Gibson and Ananthan Sadagopan describe a novel modality within induced proximity therapeutics: Targeted Protein Relocalization. They developed small molecules that leverage the nuclear-localized protein BRD4 to transport cytosolic proteins into the nucleus. In one example, they showed the nuclear relocalization of mutant NPM1c, a protein that is mislocalized into the cytosol due to genetic mutations in AML. They also showed that these small molecules can be used to increase transcription of DNA binding proteins due to recruitment of the transcriptional machinery. These findings pave the way for the rewiring and restoration of cellular processes through induced proximity, with significant implications for disease therapy in cancer and other areas. Read the paper here
Farewell and Congratulations Tiki Hayes!
Tiki Hayes has been a postdoctoral scientist with the Meyerson Lab since 2017 working on structure function analysis of EGFR. She has now joined the University of California, Los Angeles as an Assistant Professor of Molecular and Medical Pharmacology.
We wish her the best and look forward to hearing about her future endeavors!
Tiki Hayes has been a postdoctoral scientist with the Meyerson Lab since 2017 working on structure function analysis of EGFR. She has now joined the University of California, Los Angeles as an Assistant Professor of Molecular and Medical Pharmacology.
We wish her the best and look forward to hearing about her future endeavors!
Publication: Cancer aneuploidies are shaped primarily by effects on tumour fitness – July, 2023
The most prevalent alterations in cancers are aneuploidies, gains and loss of whole chromosome arms. While patterns of aneuploidies are often consistent within a tumor type, the mechanisms leading to these copy-number changes, and phenotypic consequences resulting from them are not understood. To study this, Juliann Shih developed a new method, BISCUT, which utilizes telomere- and centromere-bounded copy-number alterations. to identify loci that are either selected for or against in aneuploidy. Loci identified by BISCUT were enriched for known cancer driver genes, some of which have not been detected in focal copy number events. Read the paper here.
The most prevalent alterations in cancers are aneuploidies, gains and loss of whole chromosome arms. While patterns of aneuploidies are often consistent within a tumor type, the mechanisms leading to these copy-number changes, and phenotypic consequences resulting from them are not understood. To study this, Juliann Shih developed a new method, BISCUT, which utilizes telomere- and centromere-bounded copy-number alterations. to identify loci that are either selected for or against in aneuploidy. Loci identified by BISCUT were enriched for known cancer driver genes, some of which have not been detected in focal copy number events. Read the paper here.
25th Lab Reunion Announcement
The Meyerson Lab is thrilled to announce an extraordinary event taking place this fall- the 25 year alumni reunion for our esteemed lab! In 1998 the Meyerson lab embarked on a journey to apply genomic approaches to understand the causes of human cancer. And through the years, the Meyerson Lab has shaped the minds and careers of many individuals. This landmark occasion presents a unique opportunity to reconnect, reminisce, and reignite the passion that thrives within the lab. As we gather to celebrate a quarter century of breakthroughs, collaboration, and shared knowledge, we invite former lab members to join us on October 14th & 15th, 2023 in Boston, MA. This event promises to be an exciting mix of nostalgia and camaraderie, as we honor the past and share our continued collective achievements. If you have not already done so, please email Julie at [email protected] for more information.
We look forward to welcoming alumni and lab members to this significant milestone in our shared history!
The Meyerson Lab is thrilled to announce an extraordinary event taking place this fall- the 25 year alumni reunion for our esteemed lab! In 1998 the Meyerson lab embarked on a journey to apply genomic approaches to understand the causes of human cancer. And through the years, the Meyerson Lab has shaped the minds and careers of many individuals. This landmark occasion presents a unique opportunity to reconnect, reminisce, and reignite the passion that thrives within the lab. As we gather to celebrate a quarter century of breakthroughs, collaboration, and shared knowledge, we invite former lab members to join us on October 14th & 15th, 2023 in Boston, MA. This event promises to be an exciting mix of nostalgia and camaraderie, as we honor the past and share our continued collective achievements. If you have not already done so, please email Julie at [email protected] for more information.
We look forward to welcoming alumni and lab members to this significant milestone in our shared history!
New Meyerson Lab Members in 2023
Allison Chou and Diego Capcha, and Vincent Bozinov join the lab as Research Associates. Ananya Kodali, Ethan Shurburg and Iris Lee join as Associate Computational Biologists.
Allison is joining the lab from Princeton University. She is currently working on developing novel cancer treatments for lung cancers, with targets including mutant receptor tyrosine kinases and transcription factors. In her spare time, Allison enjoys running, reading, and doing crosswords.
Diego is joining from Haverford College. He is currently attempting to leverage dsRNA-sensing pathways to develop novel cancer therapeutics. In his free time, he enjoys playing Super Smash Brothers Ultimate for the Nintendo Switch and having picnics in the Boston Common.
Vincent is joining the lab from Baylor University. He is currently working on projects involving uncovering mechanisms of manipulating telomeres, telomerase, and ALT in cancer cells and stem cells. In his free time, Vincent enjoys going to the gym, reading, painting, and 3D printing.
Ananya is joining us from the University of Texas at Austin. She is currently working to analyze targeted genomic sequencing data from oncology patients at Dana-Farber. In her free time, Ananya enjoys baking, crosswords, and cycling.
Ethan is joining us from Brandeis University. He is currently working to understand the relationship between genetic ancestry and lung cancer development. In his free time, Ethan enjoys reading, climbing, and watching Formula 1.
Iris is joining from the California Institute of Technology. She is currently working on identifying potential microbial causes of diseases and tumors such as AMD and SI-NET tumors. In her free time, Iris enjoys rock climbing, painting, and playing Catan.
Allison Chou and Diego Capcha, and Vincent Bozinov join the lab as Research Associates. Ananya Kodali, Ethan Shurburg and Iris Lee join as Associate Computational Biologists.
Allison is joining the lab from Princeton University. She is currently working on developing novel cancer treatments for lung cancers, with targets including mutant receptor tyrosine kinases and transcription factors. In her spare time, Allison enjoys running, reading, and doing crosswords.
Diego is joining from Haverford College. He is currently attempting to leverage dsRNA-sensing pathways to develop novel cancer therapeutics. In his free time, he enjoys playing Super Smash Brothers Ultimate for the Nintendo Switch and having picnics in the Boston Common.
Vincent is joining the lab from Baylor University. He is currently working on projects involving uncovering mechanisms of manipulating telomeres, telomerase, and ALT in cancer cells and stem cells. In his free time, Vincent enjoys going to the gym, reading, painting, and 3D printing.
Ananya is joining us from the University of Texas at Austin. She is currently working to analyze targeted genomic sequencing data from oncology patients at Dana-Farber. In her free time, Ananya enjoys baking, crosswords, and cycling.
Ethan is joining us from Brandeis University. He is currently working to understand the relationship between genetic ancestry and lung cancer development. In his free time, Ethan enjoys reading, climbing, and watching Formula 1.
Iris is joining from the California Institute of Technology. She is currently working on identifying potential microbial causes of diseases and tumors such as AMD and SI-NET tumors. In her free time, Iris enjoys rock climbing, painting, and playing Catan.
2023 Summer Students
This summer the Meyerson Lab had the pleasure of hosting several summer students: Mia Bilic, Alice Feng, Tong Gao, Shreya Gokhale, Kathleen Oliver, Alma Quijano, and Ananthan Sadagopan.
Mia Bilic is a student at McGill University where she is majoring in honors Biochemistry. This summer, she is working alongside David Walter researching U2AF1. In her spare time, she enjoys weightlifting, spending time with her dog, in addition to beach volleyball and playing the New York Times daily crossword puzzles.
Alice Feng is a rising sophomore at Harvard University. This summer, she worked with Alena Yermalovich to investigate protein-coding gene CMTR2’s tumorigenic potential in lung cancer. Outside the lab, she loves crafting, figure skating, and adventuring with friends.
Tong Gao is a student at Williams College studying Chemistry and Mathematics. Over the summer she worked under Anders Dohlman. Outside of the lab, she is an avid language learner, studying French, Latin, and Greek.
Shreya Gokhale is a student at the University of Michigan majoring in Biology. This summer, she worked with Kristyna Kotynkova and Sawyer Andersen to research the chemically-induced dimerization of SLFN12. Outside the lab, she enjoys reading, gymnastics, and trying new brunch spots with her friends.
Kathleen Oliver is a student majoring Business Management at Bunker Hill. This summer, she worked alongside Julie Hammond-Coiro in order to learn more about business administration and operations. In her free time, she enjoys playing tennis, reading, and studying Spanish.
Alma Quijano is a senior at Farmingdale State College where she is majoring in Bioscience. This summer, she worked under Netta Makinen where she analyzed differential gene expression data of small intestinal neuroendocrine tumors and the ileum of healthy individuals. In her free time, she likes to visit new food spots with friends, collect small trinkets, watch K-dramas, and listen to music.
Ananthan Sadagopan is a rising junior at MIT. This summer, he worked with Will Gibson to drug some of cancer's most intractable drivers. Outside the lab, he enjoys lifting and biking.
Our group of summer students have been a fantastic asset to the lab, actively contributing to several remarkable projects. We eagerly anticipate learning about their future achievements, in science and beyond!
This summer the Meyerson Lab had the pleasure of hosting several summer students: Mia Bilic, Alice Feng, Tong Gao, Shreya Gokhale, Kathleen Oliver, Alma Quijano, and Ananthan Sadagopan.
Mia Bilic is a student at McGill University where she is majoring in honors Biochemistry. This summer, she is working alongside David Walter researching U2AF1. In her spare time, she enjoys weightlifting, spending time with her dog, in addition to beach volleyball and playing the New York Times daily crossword puzzles.
Alice Feng is a rising sophomore at Harvard University. This summer, she worked with Alena Yermalovich to investigate protein-coding gene CMTR2’s tumorigenic potential in lung cancer. Outside the lab, she loves crafting, figure skating, and adventuring with friends.
Tong Gao is a student at Williams College studying Chemistry and Mathematics. Over the summer she worked under Anders Dohlman. Outside of the lab, she is an avid language learner, studying French, Latin, and Greek.
Shreya Gokhale is a student at the University of Michigan majoring in Biology. This summer, she worked with Kristyna Kotynkova and Sawyer Andersen to research the chemically-induced dimerization of SLFN12. Outside the lab, she enjoys reading, gymnastics, and trying new brunch spots with her friends.
Kathleen Oliver is a student majoring Business Management at Bunker Hill. This summer, she worked alongside Julie Hammond-Coiro in order to learn more about business administration and operations. In her free time, she enjoys playing tennis, reading, and studying Spanish.
Alma Quijano is a senior at Farmingdale State College where she is majoring in Bioscience. This summer, she worked under Netta Makinen where she analyzed differential gene expression data of small intestinal neuroendocrine tumors and the ileum of healthy individuals. In her free time, she likes to visit new food spots with friends, collect small trinkets, watch K-dramas, and listen to music.
Ananthan Sadagopan is a rising junior at MIT. This summer, he worked with Will Gibson to drug some of cancer's most intractable drivers. Outside the lab, he enjoys lifting and biking.
Our group of summer students have been a fantastic asset to the lab, actively contributing to several remarkable projects. We eagerly anticipate learning about their future achievements, in science and beyond!
Meyerson Lab Departures in 2023
This summer the Meyerson Lab will be saying its goodbyes to many of our wonderful members.
Lior Kofman was an associate computational biologist working with Andrew Cherniack for the past two years. He is now an incoming medical student at Tufts University School of Medicine.
Quinn McVeigh was a research associate working with Gizem Uzunbas for the past two years. She is now an incoming PhD student at the University of Washington School of Medicine.
Robert Shue was an associate computational biologist working with Yvonne Li for the past year. He is now an incoming medical student at Case Western Reserve University of Medicine.
Stephanie Tang was a research associate working with Jon Goldstein for the past three years. She is now an incoming medical student at the University of Pennsylvania Medical School.
Zarin Mohsenin was a research associate working with Alena Yermalovich for the past two years. She is now an incoming medical student at Sidney Kimmel Medical College.
Patrick Zhuang was a research associate working with Tao Zou for the past two years. He is now an incoming MD/PhD student at Case Western Reserve University of Medicine.
Jon Goldstein has been a research scientist with the Meyerson Lab since 2014. He is now the Director of Biology at Flare Therapeutics.
Brian Golbourn, working closely with Jon Goldstein, has been a research scientist with the Meyerson Lab for the past year. He has now joined Flare Therapeutics as a scientist.
We look forward to hearing about their future accomplishments, in science and beyond!
This summer the Meyerson Lab will be saying its goodbyes to many of our wonderful members.
Lior Kofman was an associate computational biologist working with Andrew Cherniack for the past two years. He is now an incoming medical student at Tufts University School of Medicine.
Quinn McVeigh was a research associate working with Gizem Uzunbas for the past two years. She is now an incoming PhD student at the University of Washington School of Medicine.
Robert Shue was an associate computational biologist working with Yvonne Li for the past year. He is now an incoming medical student at Case Western Reserve University of Medicine.
Stephanie Tang was a research associate working with Jon Goldstein for the past three years. She is now an incoming medical student at the University of Pennsylvania Medical School.
Zarin Mohsenin was a research associate working with Alena Yermalovich for the past two years. She is now an incoming medical student at Sidney Kimmel Medical College.
Patrick Zhuang was a research associate working with Tao Zou for the past two years. He is now an incoming MD/PhD student at Case Western Reserve University of Medicine.
Jon Goldstein has been a research scientist with the Meyerson Lab since 2014. He is now the Director of Biology at Flare Therapeutics.
Brian Golbourn, working closely with Jon Goldstein, has been a research scientist with the Meyerson Lab for the past year. He has now joined Flare Therapeutics as a scientist.
We look forward to hearing about their future accomplishments, in science and beyond!
Postdoctoral Fellowship Awardees -- July 2023
Postdoctoral fellow Mitchell Leibowitz has been awarded a 3-year NIH F32 fellowship for his proposal entitled Targeting the cancer neo-genome for destruction with CRISPR Cas-enzymes.
Postdoctoral fellow Anders Dohlman has received a 4-year fellowship from the Damon Runyon Cancer Research Foundation for his proposal "Identifying the genomic basis for Fusobacterium nucleatum's colonization of colorectal cancers".
Congratulations Mitchell and Anders!
Postdoctoral fellow Mitchell Leibowitz has been awarded a 3-year NIH F32 fellowship for his proposal entitled Targeting the cancer neo-genome for destruction with CRISPR Cas-enzymes.
Postdoctoral fellow Anders Dohlman has received a 4-year fellowship from the Damon Runyon Cancer Research Foundation for his proposal "Identifying the genomic basis for Fusobacterium nucleatum's colonization of colorectal cancers".
Congratulations Mitchell and Anders!
Congratulations to Kar-Tong Tan on completion of his thesis -- April 2023
Congratulations to Dr. Kar-Tong Tan, who successfully defended his thesis, Delineating genome alterations in cancer with long-read and linked-read sequencing, on April 27. Kar-Tong graduates from the Biological and Biomedical Sciences (BBS) Program of Harvard University.
Congratulations to Dr. Kar-Tong Tan, who successfully defended his thesis, Delineating genome alterations in cancer with long-read and linked-read sequencing, on April 27. Kar-Tong graduates from the Biological and Biomedical Sciences (BBS) Program of Harvard University.
Publication: Telomerase inhibition as a therapeutic strategy for glioblastoma treatment – January, 2023
The most common clonal oncogenic mutations in glioblastoma, one of the deadliest cancers, reside in the TERT (telomerase reverse transcriptase) promoter and upregulate its expression. Inhibition of telomerase is therefore thought to be a promising therapeutic strategy. In a new paper, Elisa Aquilanti and colleagues use CRISPR interference to knock down TERT expression in glioblastoma cell lines carrying the TERT promoter mutation to study effects on telomere length, cell viability, and tumor formation. They find that cells lose proliferative ability over time and show signs of telomere crisis, and that tumor formation is inhibited shortly after tumor implantation but not when tumor burden is high. These results suggest that telomerase inhibition may be an effective glioblastoma treatment in a low tumor burden setting, such as following surgical removal and chemoradiation.
The most common clonal oncogenic mutations in glioblastoma, one of the deadliest cancers, reside in the TERT (telomerase reverse transcriptase) promoter and upregulate its expression. Inhibition of telomerase is therefore thought to be a promising therapeutic strategy. In a new paper, Elisa Aquilanti and colleagues use CRISPR interference to knock down TERT expression in glioblastoma cell lines carrying the TERT promoter mutation to study effects on telomere length, cell viability, and tumor formation. They find that cells lose proliferative ability over time and show signs of telomere crisis, and that tumor formation is inhibited shortly after tumor implantation but not when tumor burden is high. These results suggest that telomerase inhibition may be an effective glioblastoma treatment in a low tumor burden setting, such as following surgical removal and chemoradiation.
Publication: SLFN12 digests tRNA-Leu-TAA in velcrin-treated cells -- October 2022
Velcrin compounds kill cancer cells expressing elevated levels of the phosphodiesterase, PDE3A, and the SLFN12 RNase by inducing complex formation between these two proteins. In work led by Senior Group Leader Heidi Greulich, Sooncheol (Charlie) Lee and colleagues report the discovery of the physiological substrate of the SLFN12 RNase, tRNA-Leu-TAA. Treatment of biomarker-positive cancer cells with velcrin compounds causes PDE3A-SLFN12 complex formation, upregulation of SLFN12 RNase activity, cleavage of tRNA-Leu-TAA, stalling of ribosomes at cognate TTA codons, and global inhibition of protein synthesis, resulting in cancer cell death. Read all about it here.
Velcrin compounds kill cancer cells expressing elevated levels of the phosphodiesterase, PDE3A, and the SLFN12 RNase by inducing complex formation between these two proteins. In work led by Senior Group Leader Heidi Greulich, Sooncheol (Charlie) Lee and colleagues report the discovery of the physiological substrate of the SLFN12 RNase, tRNA-Leu-TAA. Treatment of biomarker-positive cancer cells with velcrin compounds causes PDE3A-SLFN12 complex formation, upregulation of SLFN12 RNase activity, cleavage of tRNA-Leu-TAA, stalling of ribosomes at cognate TTA codons, and global inhibition of protein synthesis, resulting in cancer cell death. Read all about it here.
Publication: synthesis of potent covalent PPARγ inverse-agonists BAY-4931 and BAY-0069 -- October 2022
Previous studies from Jon Goldstein and colleagues established PPARG as an oncogenic driver of luminal bladder cancer. In a new publication, Goldstein and collaborators from the Broad Institute, Bayer AG, and Nuvisan ICB describe high-throughout screening for PPARG inverse-agonists followed by structure-informed design and hit-to-lead medicinal chemistry efforts. BAY-4931 and BAY-0069 are novel chemotypes for covalent PPARG inverse-agonists with potent and efficacious effects using in vitro PPARG-driven bladder cancer model systems. Read the paper here.
Previous studies from Jon Goldstein and colleagues established PPARG as an oncogenic driver of luminal bladder cancer. In a new publication, Goldstein and collaborators from the Broad Institute, Bayer AG, and Nuvisan ICB describe high-throughout screening for PPARG inverse-agonists followed by structure-informed design and hit-to-lead medicinal chemistry efforts. BAY-4931 and BAY-0069 are novel chemotypes for covalent PPARG inverse-agonists with potent and efficacious effects using in vitro PPARG-driven bladder cancer model systems. Read the paper here.
Anders Dohlman joins the Meyerson Lab -- September 2022
Anders Dohlman recently joined the Meyerson lab as a postdoctoral fellow. Anders recently completed his PhD in Biomedical Engineering at Duke University with Dr. Xiling Shen. His dissertation work involved the development of computational tools and resources for understanding pan-cancer host-microbe interactions. In particular, he devised analytical strategies for determining the endogenous microbial composition of tumors sequenced for The Cancer Genome Atlas (TCGA). This led to the identification of novel host-bacterial interactions in colorectal cancer and the discovery that fungi are associated with multiple human tumor types. In Matthew’s lab he will be continuing his research on host-microbe interactions in cancer. Outside the lab, he enjoys traveling, woodworking, watering his plants, and giving his cat belly-rubs.
Anders Dohlman recently joined the Meyerson lab as a postdoctoral fellow. Anders recently completed his PhD in Biomedical Engineering at Duke University with Dr. Xiling Shen. His dissertation work involved the development of computational tools and resources for understanding pan-cancer host-microbe interactions. In particular, he devised analytical strategies for determining the endogenous microbial composition of tumors sequenced for The Cancer Genome Atlas (TCGA). This led to the identification of novel host-bacterial interactions in colorectal cancer and the discovery that fungi are associated with multiple human tumor types. In Matthew’s lab he will be continuing his research on host-microbe interactions in cancer. Outside the lab, he enjoys traveling, woodworking, watering his plants, and giving his cat belly-rubs.
2022 Summer Students
This summer the Meyerson Lab had the pleasure of hosting eight summer students: Benjamin Grossman, Anaïs Killian, Emi Lundberg, Sophie Munn, Aaron Orgel, Camilla Righetti, Ananthan Sadagopan, and Max Garrity-Janger.
Benjamin Grossman is a junior at Bowdoin College interested in developing more effective cancer treatments for Non-Hodgkin's Lymphoma. In the Meyerson Lab, he worked under Dr. David Walter creating a degron system to investigate U2AF1 mutations in lung adenocarcinoma. In his free time he enjoys hanging out with friends, exploring new places and listening to music.
Anaïs Killian is a freshman at Harvard College. She is interested in studying molecular and cellular biology. During her free time, Anaïs enjoys walking along the Charles River with friends and exploring different baking shows.
Emi Lundberg is a sophomore at Emory University who worked under Dr. Guanxi Qiao investigating the relationship between Fusobacterium nucleatum and T cell lymphocytes in the colorectal cancer tumor microbiome. In her free time she enjoys spending time outdoors and reading.
Sophie Munn is a sophomore at McGill University who worked under Netta Makinen using computational methods to analyze gene expression data of small intestinal neuroendocrine tumors. In her free time she enjoys baking, spending time with friends, and reading.
Aaron Orgel is a sophomore at Vanderbilt University interested in CRISPR technology and immunology. In the Meyerson Lab, he worked under Dr. Tao Zou to determine the pathway and dependency of PACT/PKR in neuroendocrine cell lines. Outside of the lab, Aaron enjoys skiing and taking care of his beehives.
Camilla Righetti is a master student in Quantitative and Computational Biology from the University of Trento. She is interested in the analysis of genomic data and detection of new mechanisms of resistance to drugs. She is also interested in multi-omics data from single-cell analysis. In her free time, Camilla enjoys watching movies and crocheting.
Ananthan Sadagopan is a sophomore at MIT majoring in chemistry and biology. He is broadly interested in designing new therapeutic strategies to target driver mutations in cancers. He is also interested in understanding somatic perturbations of sex chromosomes in cancer. He enjoys biking and listening to music in his free time.
Max Garrity-Janger is a junior at Harvard College studying Applied Mathematics with an area of application in biology. This summer, under Kar-Tong Tan's guidance, he is using a combination of short and long read sequencing data to identify novel telomeric repeats in cancer cell lines. Outside of research and academics, he loves playing hockey and currently serves as the Vice President of Harvard's club hockey team.
All eight of the summer students have been great additions to the lab, and have contributed to some really great projects! We look forward to hearing about their future accomplishments, in science and beyond!
This summer the Meyerson Lab had the pleasure of hosting eight summer students: Benjamin Grossman, Anaïs Killian, Emi Lundberg, Sophie Munn, Aaron Orgel, Camilla Righetti, Ananthan Sadagopan, and Max Garrity-Janger.
Benjamin Grossman is a junior at Bowdoin College interested in developing more effective cancer treatments for Non-Hodgkin's Lymphoma. In the Meyerson Lab, he worked under Dr. David Walter creating a degron system to investigate U2AF1 mutations in lung adenocarcinoma. In his free time he enjoys hanging out with friends, exploring new places and listening to music.
Anaïs Killian is a freshman at Harvard College. She is interested in studying molecular and cellular biology. During her free time, Anaïs enjoys walking along the Charles River with friends and exploring different baking shows.
Emi Lundberg is a sophomore at Emory University who worked under Dr. Guanxi Qiao investigating the relationship between Fusobacterium nucleatum and T cell lymphocytes in the colorectal cancer tumor microbiome. In her free time she enjoys spending time outdoors and reading.
Sophie Munn is a sophomore at McGill University who worked under Netta Makinen using computational methods to analyze gene expression data of small intestinal neuroendocrine tumors. In her free time she enjoys baking, spending time with friends, and reading.
Aaron Orgel is a sophomore at Vanderbilt University interested in CRISPR technology and immunology. In the Meyerson Lab, he worked under Dr. Tao Zou to determine the pathway and dependency of PACT/PKR in neuroendocrine cell lines. Outside of the lab, Aaron enjoys skiing and taking care of his beehives.
Camilla Righetti is a master student in Quantitative and Computational Biology from the University of Trento. She is interested in the analysis of genomic data and detection of new mechanisms of resistance to drugs. She is also interested in multi-omics data from single-cell analysis. In her free time, Camilla enjoys watching movies and crocheting.
Ananthan Sadagopan is a sophomore at MIT majoring in chemistry and biology. He is broadly interested in designing new therapeutic strategies to target driver mutations in cancers. He is also interested in understanding somatic perturbations of sex chromosomes in cancer. He enjoys biking and listening to music in his free time.
Max Garrity-Janger is a junior at Harvard College studying Applied Mathematics with an area of application in biology. This summer, under Kar-Tong Tan's guidance, he is using a combination of short and long read sequencing data to identify novel telomeric repeats in cancer cell lines. Outside of research and academics, he loves playing hockey and currently serves as the Vice President of Harvard's club hockey team.
All eight of the summer students have been great additions to the lab, and have contributed to some really great projects! We look forward to hearing about their future accomplishments, in science and beyond!
Publication: calling errors in nanopore sequencing of highly repetitive regions like telomeres -- August 2022
Nanopore long-read genome sequencing is emerging as a potential approach for the study of genomes. Here, graduate student Kar-Tong Tan reports extensive basecalling-induced errors at telomere repeats across nanopore sequencing data for telomeres of multiple organisms, in collaboration with Dana-Farber colleague Heng Li. We further demonstrated that tuning of nanopore basecalling models, and selective application of the tuned models to telomeric reads, led to improved recovery and analysis of telomeric regions, with little detected negative impact on basecalling of other genomic regions. Read the paper here.
Nanopore long-read genome sequencing is emerging as a potential approach for the study of genomes. Here, graduate student Kar-Tong Tan reports extensive basecalling-induced errors at telomere repeats across nanopore sequencing data for telomeres of multiple organisms, in collaboration with Dana-Farber colleague Heng Li. We further demonstrated that tuning of nanopore basecalling models, and selective application of the tuned models to telomeric reads, led to improved recovery and analysis of telomeric regions, with little detected negative impact on basecalling of other genomic regions. Read the paper here.
Publication: examining structural variation in prostate cancer -- August 2022
Meng Zhou, postdoctoral fellow, together with former postdoctoral fellows Srini Viswanathan and Gavin Ha, systematically studied how structural variation has shaped the genomic landscape across different stages of prostate cancer. We generated linked-read whole genome sequencing data, and integrated public whole genome data to build a large cohort including 531 localized tumors and 143 metastatic castration-resistant prostate cancer (mCRPC) samples. We identified distinct significantly recurrent breakpoints in different disease stages, with pervasive alterations in noncoding regions flanking the AR, MYC, and FOXA1 genes enriched in mCRPC and TMPRSS2-ERG rearrangements enriched in localized prostate cancer. Read the paper here.
Meng Zhou, postdoctoral fellow, together with former postdoctoral fellows Srini Viswanathan and Gavin Ha, systematically studied how structural variation has shaped the genomic landscape across different stages of prostate cancer. We generated linked-read whole genome sequencing data, and integrated public whole genome data to build a large cohort including 531 localized tumors and 143 metastatic castration-resistant prostate cancer (mCRPC) samples. We identified distinct significantly recurrent breakpoints in different disease stages, with pervasive alterations in noncoding regions flanking the AR, MYC, and FOXA1 genes enriched in mCRPC and TMPRSS2-ERG rearrangements enriched in localized prostate cancer. Read the paper here.
Publication: identifying the origin of multifocal ileal neuroendocrine tumors -- August 2022
To better understand how small intestinal neuroendocrine tumors (SI-NETs) develop into a multifocal disease in the distal ileum, postdoctoral fellows Netta Mäkinen and Meng Zhou performed whole genome sequencing on multiple samples from 13 patients with multifocal ileal NETs. They analyzed data from synchronous primary tumors, metastases, and corresponding normal samples, looking for recurrent somatic genomic alterations, affected signaling pathways, and shared mutation signatures. They found an absence of shared somatic variation between synchronous primary tumors in each patient; in addition, multiple metastases in a patient were found to originate from either one or several primary tumors. This genomic diversity found among multifocal ileal NETs highlights the importance of developing optimized targeted treatments for this disease. Read the paper here.
To better understand how small intestinal neuroendocrine tumors (SI-NETs) develop into a multifocal disease in the distal ileum, postdoctoral fellows Netta Mäkinen and Meng Zhou performed whole genome sequencing on multiple samples from 13 patients with multifocal ileal NETs. They analyzed data from synchronous primary tumors, metastases, and corresponding normal samples, looking for recurrent somatic genomic alterations, affected signaling pathways, and shared mutation signatures. They found an absence of shared somatic variation between synchronous primary tumors in each patient; in addition, multiple metastases in a patient were found to originate from either one or several primary tumors. This genomic diversity found among multifocal ileal NETs highlights the importance of developing optimized targeted treatments for this disease. Read the paper here.
New Meyerson Lab Members in 2022
Sawyer Andersen and Kevin Jiang join the lab as Research Associates and Akansha Gupta as an Associate Computational Biologist.
Sawyer is joining us from the University of Massachusetts Amherst. He is currently working to understand the mechanisms of novel cancer therapeutics that target tumor cells expressing high levels of SLFN12. In his free time, Sawyer enjoys playing golf and spending time outside in nature.
Kevin is joining us from the University of California, Los Angeles. While at UCLA, Kevin studied the ecologic succession of the adult human gut microbiome using trajectory analysis and the regulation of the NFkB pathway in macrophages. He is currently working to understand the impact of Fusobacterium on the colorectal cancer tumor microenvironment. In his free time, Kevin enjoys watching Formula 1, playing cello, and trying new foods.
Akansha is joining us from the University of Wisconsin-Madison. Currently, her work focuses on performing genomic analyses to identify new targets for cancer therapeutics. Additionally, she analyzes copy number alterations and rearrangements for projects with the National Cancer Institute's Genomic Data Analysis Network (GDAN). Outside of the lab, Akansha enjoys reading, working on art projects, and trying new restaurants.
Sawyer Andersen and Kevin Jiang join the lab as Research Associates and Akansha Gupta as an Associate Computational Biologist.
Sawyer is joining us from the University of Massachusetts Amherst. He is currently working to understand the mechanisms of novel cancer therapeutics that target tumor cells expressing high levels of SLFN12. In his free time, Sawyer enjoys playing golf and spending time outside in nature.
Kevin is joining us from the University of California, Los Angeles. While at UCLA, Kevin studied the ecologic succession of the adult human gut microbiome using trajectory analysis and the regulation of the NFkB pathway in macrophages. He is currently working to understand the impact of Fusobacterium on the colorectal cancer tumor microenvironment. In his free time, Kevin enjoys watching Formula 1, playing cello, and trying new foods.
Akansha is joining us from the University of Wisconsin-Madison. Currently, her work focuses on performing genomic analyses to identify new targets for cancer therapeutics. Additionally, she analyzes copy number alterations and rearrangements for projects with the National Cancer Institute's Genomic Data Analysis Network (GDAN). Outside of the lab, Akansha enjoys reading, working on art projects, and trying new restaurants.
Publication: examining bacterial communities associated with esophageal squamous cell carcinoma -- July 2022
There are strong geographic patterns in the incidence of esophageal squamous cell carcinoma (ESCC) worldwide. To address whether microbial communities are associated with ESCC in high-incidence regions of the world, Jason Nomburg, who recently defended his PhD thesis in the Meyerson and DeCaprio labs, conducted an analysis of microbial communities in ESCC tumors. Jason and collaborators, including Katherine Van Loon at UCSF and Elia Mmbaga at Muhimbili University, found that bacterial genera such as Fusobacterium, which are associated with other gastrointestinal cancers, are present in ESCC tumors from patients in high-incidence regions; we also found a potential link between tumor and oral bacterial communities in some ESCC patients. Read the paper here.
There are strong geographic patterns in the incidence of esophageal squamous cell carcinoma (ESCC) worldwide. To address whether microbial communities are associated with ESCC in high-incidence regions of the world, Jason Nomburg, who recently defended his PhD thesis in the Meyerson and DeCaprio labs, conducted an analysis of microbial communities in ESCC tumors. Jason and collaborators, including Katherine Van Loon at UCSF and Elia Mmbaga at Muhimbili University, found that bacterial genera such as Fusobacterium, which are associated with other gastrointestinal cancers, are present in ESCC tumors from patients in high-incidence regions; we also found a potential link between tumor and oral bacterial communities in some ESCC patients. Read the paper here.
Matthew is elected to the American Academy of Arts and Sciences -- April 2022
Founded in 1780, the American Academy of Arts and Sciences honors excellence and convenes leaders from every field of human endeavor to examine new ideas, address issues of importance to the nation and the world, and work together. The announcement of new members can be read here, and the full list of new members can be read here.
Founded in 1780, the American Academy of Arts and Sciences honors excellence and convenes leaders from every field of human endeavor to examine new ideas, address issues of importance to the nation and the world, and work together. The announcement of new members can be read here, and the full list of new members can be read here.
Jason Nomburg successfully defends his thesis -- April 2022
Jason recently defended his thesis, titled “Using Sequencing Approaches to Characterize Tumor Microbial Communities and Viral Transcriptomes”, marking his graduation from the Virology program at Harvard. Congratulations Dr. Nomburg!
Jason recently defended his thesis, titled “Using Sequencing Approaches to Characterize Tumor Microbial Communities and Viral Transcriptomes”, marking his graduation from the Virology program at Harvard. Congratulations Dr. Nomburg!
Publication: characterizing wraparound transcription in polyomaviruses -- April 2022
Jason Nomburg, a graduate student in the Meyerson lab, along with his collaborators, compared short- and long-read RNA sequencing of eight polyomaviruses (PyV) with the goal of characterizing their transcriptomes. The authors identify pervasive wraparound transcription in PyV, wherein transcription runs through the polyA site and circles the genome multiple times. The authors identify novel, conserved transcripts such as superT, a T antigen containing two RB-binding LxCxE motifs, and find that superT-encoding transcripts are abundant in PyV-associated human cancers. Read the article here!
Jason Nomburg, a graduate student in the Meyerson lab, along with his collaborators, compared short- and long-read RNA sequencing of eight polyomaviruses (PyV) with the goal of characterizing their transcriptomes. The authors identify pervasive wraparound transcription in PyV, wherein transcription runs through the polyA site and circles the genome multiple times. The authors identify novel, conserved transcripts such as superT, a T antigen containing two RB-binding LxCxE motifs, and find that superT-encoding transcripts are abundant in PyV-associated human cancers. Read the article here!
Zhouwei Zhang successfully defends his thesis -- April 2022
Zhouwei recently defended his thesis, titled “Studies of genomic alterations and therapeutic vulnerabilities in cancers”, marking his graduation from the Program for Biological Sciences in Public Health at the Harvard T.H. Chan School of Public Health. Congratulations Dr. Zhang!
Zhouwei recently defended his thesis, titled “Studies of genomic alterations and therapeutic vulnerabilities in cancers”, marking his graduation from the Program for Biological Sciences in Public Health at the Harvard T.H. Chan School of Public Health. Congratulations Dr. Zhang!
Publication: analyzing pan-cancer CDK4/6 gene dependencies -- April 2022
Zhouwei Zhang, a graduate student in the Meyerson lab, collaborated with post-doctoral fellow Lior Golomb to investigate CDK4 and CDK6 gene dependency across human cancer cell lines. Through analysis of publicly available genome-wide loss-of-function data combined with single and dual-targeting CRISPR assays, they found differential cell proliferation vulnerability of cell lines to either CDK4 deletion alone, CDK6 deletion alone, combined CDK4/CDK6 deletion, or neither. They also found that in a subset of cancer cell lines not dependent on CDK4/6, CDK2-CCNE1 is an important alternative dependency for cell proliferation. These results help define unique cancer cell populations that might be sensitive to CDK4-selective or CDK6-selective inhibitors. Read the article here!
Zhouwei Zhang, a graduate student in the Meyerson lab, collaborated with post-doctoral fellow Lior Golomb to investigate CDK4 and CDK6 gene dependency across human cancer cell lines. Through analysis of publicly available genome-wide loss-of-function data combined with single and dual-targeting CRISPR assays, they found differential cell proliferation vulnerability of cell lines to either CDK4 deletion alone, CDK6 deletion alone, combined CDK4/CDK6 deletion, or neither. They also found that in a subset of cancer cell lines not dependent on CDK4/6, CDK2-CCNE1 is an important alternative dependency for cell proliferation. These results help define unique cancer cell populations that might be sensitive to CDK4-selective or CDK6-selective inhibitors. Read the article here!
Katherine Cho joins the Meyerson Lab -- April 2022
Katherine Cho recently joined the Meyerson lab as a Research Technician. Throughout college, at Johns Hopkins University, she worked in an immunotherapy lab that focused on anti-PD-1 and anti-TIM3 therapy as a way to treat glioblastomas. The research work she did in this lab was what really made her passionate about cancer immunology. In Matthew's lab she is interested in identifying functional HLA and TCR complexes and how cytokine production can be increased for more effective screening of such complexes. Fun fact: She loves watching videos of baby pandas when she is sad or stressed. Welcome Katherine!
Katherine Cho recently joined the Meyerson lab as a Research Technician. Throughout college, at Johns Hopkins University, she worked in an immunotherapy lab that focused on anti-PD-1 and anti-TIM3 therapy as a way to treat glioblastomas. The research work she did in this lab was what really made her passionate about cancer immunology. In Matthew's lab she is interested in identifying functional HLA and TCR complexes and how cytokine production can be increased for more effective screening of such complexes. Fun fact: She loves watching videos of baby pandas when she is sad or stressed. Welcome Katherine!
Matthew is named Charles A. Dana Chair in Human Cancer Genetics -- March 2022
Established in 1992 with a gift from the Dana Foundation, this chair was previously held by David Livingston, MD., until his passing in October 2021.
The full announcement can be seen here.
Established in 1992 with a gift from the Dana Foundation, this chair was previously held by David Livingston, MD., until his passing in October 2021.
The full announcement can be seen here.
Publication: identifying correlates of immunotherapy response in melanoma -- February 2022
Sam Freeman, a graduate student in the Meyerson and Getz labs, collaborated with Moshe Sade-Feldman in Nir Hacohen's lab to investigate factors associated with response to immune checkpoint blockade in melanoma. Using rearranged T cell receptor or Immunoglobulin sequences, they found that they could quantify T cell or B cell infiltration in RNA-Seq or whole exome data. By meta-analyzing multiple cohorts, they found that patients who had high tumor mutational burden combined with either high T or B cell infiltration had longer survival and higher response rates to immunotherapy. Using expression data, they identified multiple gene pairs consisting of a tumor-expressed gene and an immune-expressed gene that were associated with survival and response, and they validated these associations in separate cohorts. Read the article here!
Sam Freeman, a graduate student in the Meyerson and Getz labs, collaborated with Moshe Sade-Feldman in Nir Hacohen's lab to investigate factors associated with response to immune checkpoint blockade in melanoma. Using rearranged T cell receptor or Immunoglobulin sequences, they found that they could quantify T cell or B cell infiltration in RNA-Seq or whole exome data. By meta-analyzing multiple cohorts, they found that patients who had high tumor mutational burden combined with either high T or B cell infiltration had longer survival and higher response rates to immunotherapy. Using expression data, they identified multiple gene pairs consisting of a tumor-expressed gene and an immune-expressed gene that were associated with survival and response, and they validated these associations in separate cohorts. Read the article here!
Brian Golbourn joins the Meyerson Lab -- February 2022
Brian Golbourn recently joined the Meyerson lab as a Research Scientist II. During his PhD he worked on leveraging genomic studies of rare pediatric brain tumors to define the landscape of alterations and validate new therapeutic approaches. In his postdoc training, he developed mouse models of rare pediatric brain tumors to facilitate the discovery of targetable metabolic vulnerabilities. In Matthew's lab he is studying the development of biochemical and cellular-based assays to study interactions between protein and DNA that are essential to cancer cell survival. Outside of the lab, he enjoys biking, fishing, and snowboarding. Welcome Brian!
Brian Golbourn recently joined the Meyerson lab as a Research Scientist II. During his PhD he worked on leveraging genomic studies of rare pediatric brain tumors to define the landscape of alterations and validate new therapeutic approaches. In his postdoc training, he developed mouse models of rare pediatric brain tumors to facilitate the discovery of targetable metabolic vulnerabilities. In Matthew's lab he is studying the development of biochemical and cellular-based assays to study interactions between protein and DNA that are essential to cancer cell survival. Outside of the lab, he enjoys biking, fishing, and snowboarding. Welcome Brian!
Jian Carrot-Zhang joins MSKCC and Weill Cornell as an Assistant Professor -- January 2022
Congratulations to Jian on her new position and new lab at MSKCC and Weill Cornell! Jian was previously a postdoctoral researcher in the Meyerson lab. You can connect with her here or here.
Congratulations to Jian on her new position and new lab at MSKCC and Weill Cornell! Jian was previously a postdoctoral researcher in the Meyerson lab. You can connect with her here or here.
Kristyna Kotynkova joins the Meyerson Lab -- January 2022
Kristyna Kotynkova recently joined the Meyerson lab as a Research Scientist I. During her PhD she studied how cells establish a proper cell division plane during cytokinesis at the Francis Crick Institute in London. For her postdoctoral research, she worked in the lab of Neil Ganem at Boston University, where she tried to understand how cancer cells cope with aneuploidy-induced stresses with a special focus on tumor suppressor gene SPINT2 and its effect on Hippo pathway signaling. In Matthew's lab she is studying the mechanism of novel cancer therapeutics that target tumor cells expressing high levels of PDE3A and SLFN12. Outside of the lab, she enjoys hiking, birding and rock climbing. Welcome Kristy!
Kristyna Kotynkova recently joined the Meyerson lab as a Research Scientist I. During her PhD she studied how cells establish a proper cell division plane during cytokinesis at the Francis Crick Institute in London. For her postdoctoral research, she worked in the lab of Neil Ganem at Boston University, where she tried to understand how cancer cells cope with aneuploidy-induced stresses with a special focus on tumor suppressor gene SPINT2 and its effect on Hippo pathway signaling. In Matthew's lab she is studying the mechanism of novel cancer therapeutics that target tumor cells expressing high levels of PDE3A and SLFN12. Outside of the lab, she enjoys hiking, birding and rock climbing. Welcome Kristy!
Mitchell Leibowitz joins the Meyerson Lab -- January 2022
Mitchell Leibowitz recently joined the Meyerson lab as a postdoctoral fellow. He received his PhD from Harvard University working in the laboratory of David Pellman. For his PhD he discovered an unintended consequence of CRISPR/Cas9 cutting--the missegregation of a chromosome leading to DNA copy number changes and clustered rearrangements. In Matthew's lab he is working with emerging technologies to selectively treat cancers and to learn new aspects biology. Outside of the lab, he loves the outdoors, and grabbing (or cooking) a good meal and a good drink. Welcome Mitchell! We're looking forward to working with you on these exciting new projects!
Mitchell Leibowitz recently joined the Meyerson lab as a postdoctoral fellow. He received his PhD from Harvard University working in the laboratory of David Pellman. For his PhD he discovered an unintended consequence of CRISPR/Cas9 cutting--the missegregation of a chromosome leading to DNA copy number changes and clustered rearrangements. In Matthew's lab he is working with emerging technologies to selectively treat cancers and to learn new aspects biology. Outside of the lab, he loves the outdoors, and grabbing (or cooking) a good meal and a good drink. Welcome Mitchell! We're looking forward to working with you on these exciting new projects!
Congratulations to Grant Recipients -- January 2022
Postdoctoral fellow Lior Golomb was recently awarded the LCRF (Lung Cancer Research Foundation) - AstraZeneca grant. This is a two year grant which will allow Lior to investigate the role of the ER Acetyl-CoA transporter in mutant EGFR lung cancer. Read more about the grant and Lior's project here.
Postdoctoral fellow Tiki Hayes was awarded an NIH K99/R00 Pathway to Independence Award to investigate the role of HER family variants in cancer. Read more about the grant and Tiki's project here.
Postdoctoral fellow Lior Golomb was recently awarded the LCRF (Lung Cancer Research Foundation) - AstraZeneca grant. This is a two year grant which will allow Lior to investigate the role of the ER Acetyl-CoA transporter in mutant EGFR lung cancer. Read more about the grant and Lior's project here.
Postdoctoral fellow Tiki Hayes was awarded an NIH K99/R00 Pathway to Independence Award to investigate the role of HER family variants in cancer. Read more about the grant and Tiki's project here.