Neil Vasan Lab
Laboratory of Functional Cancer Genomics
Herbert Irving Comprehensive Cancer Center
Columbia University
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We study how kinases regulate
breast cancer growth and drug response.
Kinases control nearly all aspects of human biology
and are the largest druggable protein class in cancer.
We manipulate kinases using next-generation functional genomics tools
and study these effects using cell biology, biochemistry, and proteomics.
Our goal is to apply these findings to discover new drug targets to prolong the lives of breast cancer patients.
Research
Research
Turning off kinases to accelerate cancer drug discovery
Kinases are one of the most important targets in precision oncology, but the ideal kinase targets for most cancers have not been established. Determining the cellular consequences of turning off kinases has immense potential to transform our understanding of kinases and kinase inhibitors. We are deciphering how kinases regulate cancer cell function by using genome editing to turn off the activity of every kinase in the human genome. This approach will identify novel kinases for therapeutic targeting and will act as a surrogate for small-molecule inhibition to enable drug discovery. We will use this platform to interrogate how kinase activity regulates breast cancer cell growth, sensitivity to targeted therapies, and druggable gene expression. This will compress the interval between kinase hit and lead discovery from decades to years by identifying the optimal mechanisms to inhibit kinases, transforming drug development and the design of combination therapies.
Solving the PI3K mutational code to tailor PI3K inhibition in breast cancer
PIK3CA is the most frequently mutated oncogene in human cancer and PI3K inhibitors are a standard of care therapy in PIK3CA mutant breast cancer. However, in most patients, it is unknown which PI3K mutations are activating and/or drug-sensitizing. We have previously characterized double mutations in PI3K which hyperactivate PI3K resulting in increased PI3K inhibitor sensitivity (Vasan et al. Science 2019, Sivakumar...Sokol, Vasan Clin Cancer Res 2023). We now will comprehensively characterize PI3K protein variants using deep mutational scanning and structural biology. This work will define the repertoire of activating and drug-sensitive patient mutations and will guide the development of mutant-selective PI3K inhibitors.
Discovering and targeting new phosphoprotein drivers of cancer
Functional genomics has identified numerous genetic drivers of cancer, giving rise to a new generation of targeted therapies. While proteins are the primary functional machinery in cells, the vast majority of modified proteins---including phosphoproteins---lack a known kinase or biological function. We aim to illuminate this “dark phosphoproteome” by finding novel substrates of kinases using phosphoproteomics and validating frequent phosphoproteins in cancer. To this end, we have already discovered new frequently phosphorylated substrates including phosphatases, epigenetic modifiers, and metabolic enzymes, which we will functionally characterize to elucidate novel targetable phosphoprotein drivers of cancer.
Identifying and validating new biomarkers of drug resistance in breast cancer
The response to anticancer therapies is limited by drug resistance (Vasan et al. Nature 2019). Traditional approaches to investigate drug resistance use targeted gene sequencing panels which are limited and do not include many critical genes that regulate major cancer cell signaling pathways. We are performing unbiased whole exome and transcriptome sequencing of tumors from patients receiving breast cancer targeted therapies and chemotherapies, in collaboration with our clinical colleagues. This will nominate new biomarkers of therapeutic resistance and we will test these mechanisms which in the laboratory. This work will determine who does–-and does not—benefit from breast cancer therapies.
Lab Members
Lab Members
Principal Investigator
Neil Vasan, MD, PhD
Neil is a physician scientist and Assistant Professor of Medicine in the Division of Hematology and Oncology and the Herbert Irving Comprehensive Cancer Center at Columbia University Irving Medical Center. He received his AB/AM from Harvard University and MD/PhD from Yale University School of Medicine, and completed clinical training in internal medicine at Massachusetts General Hospital and in medical oncology at Memorial Sloan Kettering Cancer Center. As a postdoctoral fellow, he identified double PIK3CA mutations as an oncogenic alteration, which has gone from bench to bedside as a cancer genomic biomarker. His research awards include the NIH Director's New Innovator Award (DP2), NCI Mentored Clinical Scientist Development Award (K08), AACR NextGen Star, and ASCI Young Physician-Scientist Award. He has also received research funding from Susan G. Komen, Breast Cancer Alliance, and Gilead. Neil is an active clinical oncologist treating patients with breast cancer, and serves as the Scientific Advisor for the PIK3CA Pathbreakers patient advocacy group, and as a standing member of the Oncologic Drugs Advisory Committee (ODAC) for the FDA.
Postdoctoral Fellows
Hanna Karvonen, PhD
Recipient of EMBO Postdoctoral Fellowship
Hanna received her PhD in cell and molecular biology from Tampere University, Finland, in the lab of Daniela Ungureanu where she studied the role of ROR1 pseudokinase signaling in B-cell malignancies and ovarian cancer and aimed to identify drugs that could work in combination with ROR1-targeted cancer therapies. In the Vasan lab, her research focuses on understanding how kinases regulate cancer cell growth using genome editing screens.
Remkes Scheele, PhD
Remkes Scheele obtained his BSc in Life Science and Technology from the University of Groningen. During his MSc, he performed graduate internships in the laboratories of Gerard Roelfes and Frances Arnold on artificial metalloenzymes and tryptophan synthase evolution, respectively. Remkes went on to complete his PhD in droplet microfluidics in the Hollfelder group at the University of Cambridge. Currently, Remkes is involved in genome editing screens to uncover vulnerabilities for cancer therapeutics.
Laboratory Technician and Manager
Ruchita Rathod, MS
Ruchita received her master's degree in Pharmaceutical Sciences from St. John’s University, New York, USA. She worked on the Bone Morphogenic Protein (BMP) signaling pathway. She then worked at the Memorial Sloan Kettering Cancer Center and Weill Cornell in Dr. Lewis Cantley’s lab as a research assistant assisting Dr. Neil Vasan in investigating genetic heterogeneity in tumors with PIK3CA mutations.
Fun fact: I enjoy relieving stress through cooking and baking. I love dancing to Bollywood music.
Undergraduate Students
Sophia Abrahamson
Sophia is a junior at Columbia College where she is majoring in Biochemistry. She has a long-standing interest in oncology research, having interned in Los Angeles at labs focusing on rhabdoid tumors and salivary gland cancer. Sophia is an intern at the lab, where she has continued her research in the Vasan Lab exploring the proteomic basis of breast cancer with Remkes.
Ananya Raghavan
Ananya is majoring in biomedical engineering at Columbia University. She is interested in studying cancer biology and hopes to be a physician or physician-scientist in the future. In the lab, she is working with Ali to understand the function of PIK3CA mutations using high throughput techniques. In her free time, she can be found painting, playing with her Goldendoodle Copper, or watching Bollywood.
Maya Schonberg
Maya is a sophomore at Barnard College majoring in biology. Having worked in the Vasan Lab since high school, Maya is passionate about cancer research and hopes to pursue a career in the field. In the lab, she is working with Hanna on her research on CRISPR-Cas9 editing. Outside of the lab, she loves music, exploring the city’s food landscape and spending time with her two Shih Tzus.
Clinician Scientists
Ben Herzberg, MD
Dr. Herzberg is a thoracic oncologist and Assistant Professor of Medicine at Columbia University Irving Medical Center (CUIMC). He received his AB from Princeton University, an MD from the combined Harvard Medical School and MIT Program in Health Sciences and Technology (HST), and an MSc in the History of Science and Medicine from Imperial College, London. He completed his residency in internal medicine at Massachusetts General Hospital, where he was a Stanbury Physician-Scientist trainee, and fellowship in medical oncology at Memorial Sloan-Kettering Cancer Center, where he was Chief Fellow.
His research interests are in lung cancer and cancers with special difficulties repairing damage to their DNA. He develops clinical trials using novel agents targeting DNA repair, bringing these drugs directly to my patients in the clinic. His laboratory work aims to define new vulnerabilities in cancer cells which can be leveraged for more effective, less toxic therapy. This work has been recognized by several awards from the NIH and other organizations.
Julia McGuinness, MD
Dr. McGuinness is a breast oncologist and Assistant Professor of Medicine at Columbia University Irving Medical Center (CUIMC). She serves as the PI for multiple clinical trials at CUIMC that evaluate novel treatments for patients with breast cancer. She received her BA in Biology from Williams College, and her MD from Baylor College of Medicine. She completed both her Internal Medicine residency and Hematology/Oncology fellowship at CUIMC where she served as Chief Fellow. She also completed a Postdoctoral Research Fellowship in Biomedical Informatics at CUIMC and an MPH from the Columbia University Mailman School of Public Health.
She has received numerous awards and grants including the American Society of Clinical Oncology (ASCO) Young Investigator Award, ASCO Career Development Award, and Susan G. Komen Career Catalyst Research Award. She collaborates with the Vasan Lab to analyze clinical samples from patients receiving PI3K inhibitors.
Medical Students
Abiha Kazmi
Abiha is a first year medical student at SUNY Downstate Health Sciences University. As a high school student she worked with Neil Vasan in the laboratory of Jose Baselga at Memorial Sloan Kettering Cancer Center where, as a recipient of the PBS and Stand Up to Cancer (SU2C) Emperor Science Award, she contributed to their discovery of double PIK3CA mutations. She graduated in 2023 from the Macaulay Honors College at CUNY Brooklyn College, where she majored in sociology and biology and was inducted into Phi Beta Kappa. Abiha also received the Barry M. Goldwater Scholarship in 2021.
Alumni
Alison Kearney, PhD (Scientist at Vow)
Select Publications
Select Publications
Kearney AL and Vasan N. A New Wave of PI3Kα Inhibitors. Cancer Discov 2023 13:2313-2315. Link
Sivakumar S, Jin DX, Rathod R, Ross J, Cantley LC, Scaltriti M, Chen J, Hutchinson KE, Wilson TR, Sokol ES*, Vasan N*. Genetic heterogeneity and tissue-specific patterns of tumors with multiple PIK3CA mutations. Clinical Cancer Research 2023 29:1125-1136. Link
Vasan N and Cantley LC. At a crossroad: how to translate the roles of PI3K in oncogenic and metabolic signalling into improvements in cancer therapy. Nat Rev Clin Oncol 2022 19:471-485. Link
Vasan N, Razavi P, Johnson JL, Shao H, Shah H, Antoine A, Ladewig E, Gorelick A, Lin TY, Toska E, Xu G, Kazmi A, Chang MT, Taylor BS, Dickler MN, Jhaveri K, Chandarlapaty S, Rabadan R, Reznik E, Smith ML, Sebra R, Schimmoller F, Wilson TR, Friedman LS, Cantley LC, Scaltriti M*, Baselga J*. Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kα inhibitors. Science 2019 366:714-723. Link
Vasan N, Hyman DM, and Baselga, J. A view on drug resistance in cancer. Nature 2019 575:299-309. Link
Jobs and collaborative opportunities
Jobs and collaborative opportunities
We are looking for highly motivated graduate students, postdoctoral scientists, and clinical collaborators to lead multidisciplinary studies in the areas of cancer cell signaling.
Graduate Student
Graduate students in the Coordinated Doctoral Programs in Biomedical Sciences at Columbia University are welcome to email Dr. Neil Vasan for research rotations.
Postdoctoral Scientist
We look for highly motivated candidates with prior experience in any one of the following areas to lead consequential and innovative research projects: 1) deep mutational scanning; 2) CRISPR genome editing, 3) functional (phospho)proteomics; 3) computational clinical proteomics. If you are interested to join our vibrant team, please send your CV and cover letter with a brief description of research interests to Dr. Neil Vasan.
Clinical Collaborators
We are interested in working with surgeons, radiation oncologists, and pathologists, as well as fellows, residents, and medical students to collect and annotate breast cancer clinical patient samples.
Funding
Funding
We are grateful to receive funding from many governmental and philanthropic organizations.
If you would like to donate to the Vasan Lab or the Breast Cancer program at CUIMC, please contact our Development Office.
News and Media
News and Media
Neil speaks about laboratory research, targeted therapies, and breast cancer clinical trials for international, national, and local scientific and lay audiences.
Official launch of PIK3CA Pathbreakers, a new patient advocacy organization for which Neil serves as Scientific Advisor (12/2023)
Congratulations to Sophia Abrahamson on being elected to the Columbia Phi Beta Kappa Junior 24! (12/2023).
Congratulations to Maya Schonberg on being selected to the Barnard Summer Research Institute! (5/2023)
Congratulations to Dr. Alison Kearney on receiving the American Australian Association Graduate Education Scholarship! (6/2022)
Invited seminar for Labroots (12/1/20)
Innovation in Cancer Infomatics Summit (1/23/20)
Living Beyond Breast Cancer Conference (4/24/19)
Contact information
Contact information
Irving Cancer Research Center
1130 St. Nicholas Avenue
Room 321A
New York, NY 10032
Administrative Assistant:
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