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.
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.
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.
Recent Scientific Presentations -- December 2021
The Meyerson lab was well represented at this year's Broad retreat (Dec 13-16)! Lab members presented scientific posters on drug development (presenters included Charlie Lee, Gizem Karsli Uzunbas, Jon Goldstein, Joseph McGaunn, Quinn McVeigh, and Stephanie Hoyt), and telomere long-read sequencing (Kar-Tong Tan). Quinn McVeigh also shared a poster for the affinity group she co-chairs, Accessibility@Broad. Lauren Kageler, Joseph McGaunn and Stephanie Tang led discussions on their work with the 'Societally Engaged Scientist' program at the Broad.
Lauren Kageler and Kar-Tong Tan also had the opportunity to talk about their work on TERT and telomere long-read sequencing, respectively, at the recent (Dec 14-17) Cold Spring Harbor Laboratory 'Telomeres and Telomerase' meeting.
Congratulations to all on their successful presentations and all the research that went into them! We look forward to upcoming publications and future presentations.
The Meyerson lab was well represented at this year's Broad retreat (Dec 13-16)! Lab members presented scientific posters on drug development (presenters included Charlie Lee, Gizem Karsli Uzunbas, Jon Goldstein, Joseph McGaunn, Quinn McVeigh, and Stephanie Hoyt), and telomere long-read sequencing (Kar-Tong Tan). Quinn McVeigh also shared a poster for the affinity group she co-chairs, Accessibility@Broad. Lauren Kageler, Joseph McGaunn and Stephanie Tang led discussions on their work with the 'Societally Engaged Scientist' program at the Broad.
Lauren Kageler and Kar-Tong Tan also had the opportunity to talk about their work on TERT and telomere long-read sequencing, respectively, at the recent (Dec 14-17) Cold Spring Harbor Laboratory 'Telomeres and Telomerase' meeting.
Congratulations to all on their successful presentations and all the research that went into them! We look forward to upcoming publications and future presentations.
New Meyerson Lab Members in 2021
Zarin Mohsenin and Patrick Zhuang join the lab as Research Associates, Lior Kofman as an Associate Computational Biologist and Guanxi Qiao as a postdoctoral fellow.
Zarin joins us from Haverford College where she worked in the Johnson Lab developing an approach for editing the chloroplast genome of a single-celled algae. In the Meyerson Lab, she works with Alena Yermalovich to better understand the role of the gene CMTR2 in lung cancer. In her free time, Zarin enjoys reading, hiking, and playing soccer.
Patrick is joining us from Williams College. He was a member of the Thomas Smith Lab in which he focused on using aldol reactions to stereoselectively synthesize molecules leading to the synthesis of enigmazole, a potentially tumor-suppressing molecule. In his free time, Patrick swims, plays the guitar, and enjoys spending time in a park. He is going to work with Tao Zou to develop novel therapeutic strategies to target innate immune signaling pathways that regulate cancer cell viability.
Lior is joining us from Tufts University. As a member of the Tufts Bioinformatics and Computational Biology Research Group, he modeled gene regulatory networks to understand gene interactions induced by neurological disorders and determined drug repositioning candidates using a recommender system. During his free time, Lior enjoys playing basketball, snowboarding, and reading books about the brain. Supervised by Andy Cherniack, he will be working with Blake Sanders to identify the role of Fusobacterium in colorectal cancer and with Gizem Karsli Uzunbas to identify potential gene targets in small cell lung cancer.
Guanxi is joining us from Roswell Park Comprehensive Cancer Center. There, she was a Ph.D. student of Elizabeth Repasky’s lab where she studied how stress suppresses anti-tumor immune response. Outside of lab, Guanxi enjoys reading, playing piano, and exploring new restaurant. Her research will focus on how fusobacterium affects anti-tumor immunity in colorectal cancer.
Zarin Mohsenin and Patrick Zhuang join the lab as Research Associates, Lior Kofman as an Associate Computational Biologist and Guanxi Qiao as a postdoctoral fellow.
Zarin joins us from Haverford College where she worked in the Johnson Lab developing an approach for editing the chloroplast genome of a single-celled algae. In the Meyerson Lab, she works with Alena Yermalovich to better understand the role of the gene CMTR2 in lung cancer. In her free time, Zarin enjoys reading, hiking, and playing soccer.
Patrick is joining us from Williams College. He was a member of the Thomas Smith Lab in which he focused on using aldol reactions to stereoselectively synthesize molecules leading to the synthesis of enigmazole, a potentially tumor-suppressing molecule. In his free time, Patrick swims, plays the guitar, and enjoys spending time in a park. He is going to work with Tao Zou to develop novel therapeutic strategies to target innate immune signaling pathways that regulate cancer cell viability.
Lior is joining us from Tufts University. As a member of the Tufts Bioinformatics and Computational Biology Research Group, he modeled gene regulatory networks to understand gene interactions induced by neurological disorders and determined drug repositioning candidates using a recommender system. During his free time, Lior enjoys playing basketball, snowboarding, and reading books about the brain. Supervised by Andy Cherniack, he will be working with Blake Sanders to identify the role of Fusobacterium in colorectal cancer and with Gizem Karsli Uzunbas to identify potential gene targets in small cell lung cancer.
Guanxi is joining us from Roswell Park Comprehensive Cancer Center. There, she was a Ph.D. student of Elizabeth Repasky’s lab where she studied how stress suppresses anti-tumor immune response. Outside of lab, Guanxi enjoys reading, playing piano, and exploring new restaurant. Her research will focus on how fusobacterium affects anti-tumor immunity in colorectal cancer.
Publication: investigating the activity of Telomerase in Glioblastoma
Elisa Aquilanti, an Instructor in Medicine in the Meyerson Lab, recently published a review of telomerase as a therapeutic target in glioblastoma. Glioblastoma generally has few oncogenic mutations; however, TERT promoter mutations have been found in 80% of glioblastoma samples. These mutations allow tumors to gain cellular immortality, which could be combated by telomerase inhibitors through the maintenance of telomere length. Elisa, along with Lauren Kageler, Patrick Wen and Matthew Meyerson, presents clinical and genomic data suggesting telomerase as a potential "Achilles' heel" for glioblastoma, summarizes previous experience with anti-telomerase agents, and proposes new directions for this target. Read the article here!
Elisa Aquilanti, an Instructor in Medicine in the Meyerson Lab, recently published a review of telomerase as a therapeutic target in glioblastoma. Glioblastoma generally has few oncogenic mutations; however, TERT promoter mutations have been found in 80% of glioblastoma samples. These mutations allow tumors to gain cellular immortality, which could be combated by telomerase inhibitors through the maintenance of telomere length. Elisa, along with Lauren Kageler, Patrick Wen and Matthew Meyerson, presents clinical and genomic data suggesting telomerase as a potential "Achilles' heel" for glioblastoma, summarizes previous experience with anti-telomerase agents, and proposes new directions for this target. Read the article here!
2021 Summer Students
This summer the Meyerson Lab has had the pleasure of hosting four summer students: Elise Layne, Hope Wei, Emanuele Rovera and Max Garrity-Janger.
Elise is a rising senior at Swarthmore College. This summer she is working under the direction of Dr. Tiki Hayes and is focused on the characterization of epidermal growth factor receptor (EGFR) variants in lung cancer. Outside of the lab she spends a majority of her free time sewing, playing tennis, and spending time with her dog, Walter.
Hope is currently a senior at Boston University working under Dr. Tao Zou on innate immune signaling in cancer cells and immunotherapy. A fun fact about Hope is that her favorite animal is the Great White Shark, and she is super passionate about mental health and wellbeing and ending the stigma around it.
Emanuele is working with Blake Sanders, and his research is focused on understanding the role of microbiota in colorectal cancer tumorigenesis, with the goal of elucidating its impact on patients' prognosis and response to therapies. He is currently attending the 5th year of the MD/PhD program at University of Turin, Italy.
Max is a rising junior (class of 2023) 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. These repeats coincide with structural variants such as chromosomal breaks or arm fusions within these cell lines and play an important and poorly understood role in cancer genome chromosomal rearrangements. Outside of research and academics, he loves playing hockey and currently serves as the Vice President of Harvard's club hockey team.
All four 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 has had the pleasure of hosting four summer students: Elise Layne, Hope Wei, Emanuele Rovera and Max Garrity-Janger.
Elise is a rising senior at Swarthmore College. This summer she is working under the direction of Dr. Tiki Hayes and is focused on the characterization of epidermal growth factor receptor (EGFR) variants in lung cancer. Outside of the lab she spends a majority of her free time sewing, playing tennis, and spending time with her dog, Walter.
Hope is currently a senior at Boston University working under Dr. Tao Zou on innate immune signaling in cancer cells and immunotherapy. A fun fact about Hope is that her favorite animal is the Great White Shark, and she is super passionate about mental health and wellbeing and ending the stigma around it.
Emanuele is working with Blake Sanders, and his research is focused on understanding the role of microbiota in colorectal cancer tumorigenesis, with the goal of elucidating its impact on patients' prognosis and response to therapies. He is currently attending the 5th year of the MD/PhD program at University of Turin, Italy.
Max is a rising junior (class of 2023) 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. These repeats coincide with structural variants such as chromosomal breaks or arm fusions within these cell lines and play an important and poorly understood role in cancer genome chromosomal rearrangements. Outside of research and academics, he loves playing hockey and currently serves as the Vice President of Harvard's club hockey team.
All four 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: identifying somatic and germline alterations in Renal Medullary Carcinomas
Kar-Tong Tan, a graduate student at Harvard in the Meyerson Lab, recently published a paper to determine the germline haplotypes and somatic alterations that occurred in Renal Medullary Carcinoma (RMC), a cancer restricted to young Africans and linked with the sickle cell trait. Using previously identified samples, Tan and his collaborators showed that the sickle cell haplotype in patients with RMC originated from three areas of Africa and found that the sickle cell mutation was the only candidate variant. They also found that structural variants in SMARCB1 with small or no regions of homology were the most common somatic alteration. This paper produced novel results in describing the founder population of the RMC haplotype and provides an example of how haplotype-based analyses can find high-risk variants and highly resolve structural variants. Along with Kar-Tong, group member Jian Carrot-Zhang and former member Hyunji Kim contributed to the paper. Find the article here!
Kar-Tong Tan, a graduate student at Harvard in the Meyerson Lab, recently published a paper to determine the germline haplotypes and somatic alterations that occurred in Renal Medullary Carcinoma (RMC), a cancer restricted to young Africans and linked with the sickle cell trait. Using previously identified samples, Tan and his collaborators showed that the sickle cell haplotype in patients with RMC originated from three areas of Africa and found that the sickle cell mutation was the only candidate variant. They also found that structural variants in SMARCB1 with small or no regions of homology were the most common somatic alteration. This paper produced novel results in describing the founder population of the RMC haplotype and provides an example of how haplotype-based analyses can find high-risk variants and highly resolve structural variants. Along with Kar-Tong, group member Jian Carrot-Zhang and former member Hyunji Kim contributed to the paper. Find the article here!
Publication: characterizing PDE3A and SLFN12 complex formation
Xiaoyun Wu, a senior scientist in the Greulich and Meyerson groups at the Broad Institute, collaborated with Colin Garvie of the Center for the Development of Therapeutics at the Broad Institute to characterize the small molecule-induced interaction between two cellular proteins, PDE3A and SLFN12, that results in killing of cancer cells expressing elevated levels of these two proteins. They furthermore discovered that SLFN12 is an RNase, that SLFN12 RNase activity is upregulated by PDE3A binding, and that SLFN12 RNase activity is required for cancer cell response to this family of small molecules, now called "velcrins". These results will facilitate therapeutic development of velcrins, currently in clinical trials. Additional current group members who contributed to this research include Sooncheol Lee, Stephanie Hoyt, Joseph McGaunn, and Andrew Cherniack. Read the paper here!
Xiaoyun Wu, a senior scientist in the Greulich and Meyerson groups at the Broad Institute, collaborated with Colin Garvie of the Center for the Development of Therapeutics at the Broad Institute to characterize the small molecule-induced interaction between two cellular proteins, PDE3A and SLFN12, that results in killing of cancer cells expressing elevated levels of these two proteins. They furthermore discovered that SLFN12 is an RNase, that SLFN12 RNase activity is upregulated by PDE3A binding, and that SLFN12 RNase activity is required for cancer cell response to this family of small molecules, now called "velcrins". These results will facilitate therapeutic development of velcrins, currently in clinical trials. Additional current group members who contributed to this research include Sooncheol Lee, Stephanie Hoyt, Joseph McGaunn, and Andrew Cherniack. Read the paper here!
Publication: identifying esophageal squamous cell carcinoma dependencies
Zhouwei Zhang, a graduate student with Dr. Meyerson, in collaboration with the lab of Dr. Adam Bass, identified key dependencies in esophageal squamous cell carcinoma (ESCC) using genomic dependency and pharmaceutical screening datasets. Zhouwei and colleagues found that ESCC cell lines are sensitive to ERBB inhibitors. They also found that combined inhibition of ERBB proteins and CDK4/6 (a known dependency) may synergize to kill ESCC cells, suggesting a clinical trial option that could be investigated using FDA-approved drugs. Furthermore, they showed that KLF5 facilitates activation of ERBBs in ESCC, making it a candidate biomarker for such a therapeutic strategy. Read the paper here!
Zhouwei Zhang, a graduate student with Dr. Meyerson, in collaboration with the lab of Dr. Adam Bass, identified key dependencies in esophageal squamous cell carcinoma (ESCC) using genomic dependency and pharmaceutical screening datasets. Zhouwei and colleagues found that ESCC cell lines are sensitive to ERBB inhibitors. They also found that combined inhibition of ERBB proteins and CDK4/6 (a known dependency) may synergize to kill ESCC cells, suggesting a clinical trial option that could be investigated using FDA-approved drugs. Furthermore, they showed that KLF5 facilitates activation of ERBBs in ESCC, making it a candidate biomarker for such a therapeutic strategy. Read the paper here!
Quinn McVeigh joins the Meyerson Lab!
Quinn McVeigh is joining us from University of Minnesota. There, she was a member of Nobuaki Kikyo’s lab where she studied the relationship between ER stress and fibroblast to neuron conversion. Outside of lab, Quinn enjoys baking, reading, and mountain biking. She will be working with Gizem Karsli Uzunbas to develop novel targeting approaches for lung cancer.
Quinn McVeigh is joining us from University of Minnesota. There, she was a member of Nobuaki Kikyo’s lab where she studied the relationship between ER stress and fibroblast to neuron conversion. Outside of lab, Quinn enjoys baking, reading, and mountain biking. She will be working with Gizem Karsli Uzunbas to develop novel targeting approaches for lung cancer.
Publication: characterizing EGFR mutations in lung adenocarcinoma
Netta Mäkinen, a post-doctoral fellow, and colleagues used high-throughput sequencing to study genomic evolution in tissues from a lung adenocarcinoma patient with a germline EGFR T790M mutation. Netta found that somatic EGFR mutations are early events in the pathogenesis of lung adenocarcinomas arising in the context of germline EGFR T790M. Furthermore, synchronous AAH lesions seem to represent independent neoplastic foci. Read the paper here!
Netta Mäkinen, a post-doctoral fellow, and colleagues used high-throughput sequencing to study genomic evolution in tissues from a lung adenocarcinoma patient with a germline EGFR T790M mutation. Netta found that somatic EGFR mutations are early events in the pathogenesis of lung adenocarcinomas arising in the context of germline EGFR T790M. Furthermore, synchronous AAH lesions seem to represent independent neoplastic foci. Read the paper here!
Publication: identifying T cell epitopes
Mark Lee, a post-doctoral fellow and MGH Transfusion Medicine physician, developed a new technique to identify T cell epitopes by combining cytokine-capturing antigen-presenting cells with highly complex DNA arrays encoding peptide libraries. Mark used this method to identify previously unknown targets of CD8+ and CD4+ T cell receptors that are commonly found in peripheral blood. Next step: identification of targets of tumor-infiltrating T cells. Read the paper here!
Mark Lee, a post-doctoral fellow and MGH Transfusion Medicine physician, developed a new technique to identify T cell epitopes by combining cytokine-capturing antigen-presenting cells with highly complex DNA arrays encoding peptide libraries. Mark used this method to identify previously unknown targets of CD8+ and CD4+ T cell receptors that are commonly found in peripheral blood. Next step: identification of targets of tumor-infiltrating T cells. Read the paper here!
Publication: analyzing SARS-CoV-2 transcriptomes
Jason Nomburg, a joint graduate student with Dr. Meyerson and Dr. James DeCaprio, conducted an integrative analysis of SARS-CoV-2 transcriptomes to characterize the RNA species present during infection. Jason found that SARS-CoV-2 produces non-canonical RNA species in a variety of different infection settings. These alternative transcripts may be important in the virus life cycle. Read the paper here!
Jason Nomburg, a joint graduate student with Dr. Meyerson and Dr. James DeCaprio, conducted an integrative analysis of SARS-CoV-2 transcriptomes to characterize the RNA species present during infection. Jason found that SARS-CoV-2 produces non-canonical RNA species in a variety of different infection settings. These alternative transcripts may be important in the virus life cycle. Read the paper here!
Publication: characterizing the relationship of Native American ancestry and EGFR mutations
Jian Carrot-Zhang, post-doctoral fellow, and colleagues developed a new technique to compare somatic genome alterations with ancestry analyses using tumor-only sequence data, working with Dr. Sasha Gusev in Dana-Farber’s Data Sciences Department. By studying 1,153 lung cancers from Latin American patients, in collaboration with Dr. Andres Cardona in Bogota, Colombia, and Dr. Oscar Arrieta in Mexico City, they determined that Native American ancestry in this patient population was associated with increased EGFR mutation frequency, regardless of smoking status. From this work, we can deepen our understanding of potential lung cancer risk factors. Next steps: see if we can find an inherited locus. Read the paper here!
Jian Carrot-Zhang, post-doctoral fellow, and colleagues developed a new technique to compare somatic genome alterations with ancestry analyses using tumor-only sequence data, working with Dr. Sasha Gusev in Dana-Farber’s Data Sciences Department. By studying 1,153 lung cancers from Latin American patients, in collaboration with Dr. Andres Cardona in Bogota, Colombia, and Dr. Oscar Arrieta in Mexico City, they determined that Native American ancestry in this patient population was associated with increased EGFR mutation frequency, regardless of smoking status. From this work, we can deepen our understanding of potential lung cancer risk factors. Next steps: see if we can find an inherited locus. Read the paper here!
Matthew Meyerson elected as a Fellow of the American Association for the Advancement of Science
Matthew Meyerson was elected as a Fellow by the AAAS Council for his significant contributions to the advancement of science or its applications. Fellows are selected from a diverse array of fields, including technology, academia, research, and government. Read more about the honor here!
Matthew Meyerson was elected as a Fellow by the AAAS Council for his significant contributions to the advancement of science or its applications. Fellows are selected from a diverse array of fields, including technology, academia, research, and government. Read more about the honor here!