Person
Nissim, Sahar
|
|
Biography and Research Interest
BIOGRAPHY:
Dr. Nissim received his M.D. and Ph.D. from Harvard Medical School and completed his residency in Internal Medicine and fellowship in Gastroenterology at Brigham and Women’s Hospital. He has trained in Cancer Genetics and Prevention at the Dana-Farber Cancer Institute with a focus on pancreatic cancer.
His research contributions have been recognized through multiple awards including a National Pancreas Foundation Award (2012), the Burroughs Wellcome Fund Career Award for Medical Scientists (2015), the Augustyn Award in Digestive Cancer from the American Gastroenterological Association (2017), and the American Society for Clinical Investigation Young Physician-Scientist Award (2017).
He is a faculty member at The Harvard-MIT Program in Health Sciences and Technology (HST), the Hale Family Research Center, the Harvard Digestive Disease Center, and a practicing clinician at Dana Farber Cancer Institute with a focus on pancreatic cancer prevention.
Pancreatic cancer is one of the most deadly cancers, with notoriously ineffective treatment options. Our research group leverages developmental biology, genetic discovery in hereditary pancreatic cancer families, transcriptomic and proteomic approaches, and pre-clinical studies in zebrafish and mouse models to characterize novel determinants of cancer initiation and develop strategies for prevention and treatment of pancreatic cancer.
RESEARCH INTERESTS:
In about 10% of cases, pancreatic cancer occurs as multiple cases in a single family, raising suspicion of a hereditary cause. The explanation for most of these families has not been identified. Finding and understanding the genetic basis of “unsolved” pancreatic cancer families can help identify who is at risk and should have surveillance in the family. More broadly, understanding how a single inherited mutation leads to pancreatic cancer can gives us precious clues into why the cancer happens and new strategies for treatment and prevention. To address this need, the Nissim Lab has developed a research pipeline for discovery, validation, and characterization of new genetic causes of hereditary pancreatic cancer. By whole genome sequencing analysis, we can identify inherited mutations associated with pancreatic cancer in multiple family relatives. To validate the causality of these mutations in cancer, we assess how these mutations impact cancer risk in zebrafish populations. To characterize these novel cancer pathways, we interrogate function in the context of zebrafish pancreas development in conjunction with unbiased transcriptomic and proteomic approaches. As a proof-of-principle, we recently identified the cause of pancreatic cancer in a previously-unsolved family with 5 cases, validated the causality of this mutation in zebrafish populations, and discovered that the mutation alters the intracellular trafficking of KRAS (Nissim et al., Nature Genetics, 2019). We are now exploring the therapeutic potential of targeting this pathway in pancreatic cancer.
Sitting at this intersection of longitudinal care of hereditary pancreatic cancer families in the clinic, genome analysis, and zebrafish cancer models at the lab bench, our research group is well-positioned to continue making pivotal discoveries that will advance our understanding and management of pancreatic cancer.
Dr. Nissim received his M.D. and Ph.D. from Harvard Medical School and completed his residency in Internal Medicine and fellowship in Gastroenterology at Brigham and Women’s Hospital. He has trained in Cancer Genetics and Prevention at the Dana-Farber Cancer Institute with a focus on pancreatic cancer.
His research contributions have been recognized through multiple awards including a National Pancreas Foundation Award (2012), the Burroughs Wellcome Fund Career Award for Medical Scientists (2015), the Augustyn Award in Digestive Cancer from the American Gastroenterological Association (2017), and the American Society for Clinical Investigation Young Physician-Scientist Award (2017).
He is a faculty member at The Harvard-MIT Program in Health Sciences and Technology (HST), the Hale Family Research Center, the Harvard Digestive Disease Center, and a practicing clinician at Dana Farber Cancer Institute with a focus on pancreatic cancer prevention.
Pancreatic cancer is one of the most deadly cancers, with notoriously ineffective treatment options. Our research group leverages developmental biology, genetic discovery in hereditary pancreatic cancer families, transcriptomic and proteomic approaches, and pre-clinical studies in zebrafish and mouse models to characterize novel determinants of cancer initiation and develop strategies for prevention and treatment of pancreatic cancer.
RESEARCH INTERESTS:
In about 10% of cases, pancreatic cancer occurs as multiple cases in a single family, raising suspicion of a hereditary cause. The explanation for most of these families has not been identified. Finding and understanding the genetic basis of “unsolved” pancreatic cancer families can help identify who is at risk and should have surveillance in the family. More broadly, understanding how a single inherited mutation leads to pancreatic cancer can gives us precious clues into why the cancer happens and new strategies for treatment and prevention. To address this need, the Nissim Lab has developed a research pipeline for discovery, validation, and characterization of new genetic causes of hereditary pancreatic cancer. By whole genome sequencing analysis, we can identify inherited mutations associated with pancreatic cancer in multiple family relatives. To validate the causality of these mutations in cancer, we assess how these mutations impact cancer risk in zebrafish populations. To characterize these novel cancer pathways, we interrogate function in the context of zebrafish pancreas development in conjunction with unbiased transcriptomic and proteomic approaches. As a proof-of-principle, we recently identified the cause of pancreatic cancer in a previously-unsolved family with 5 cases, validated the causality of this mutation in zebrafish populations, and discovered that the mutation alters the intracellular trafficking of KRAS (Nissim et al., Nature Genetics, 2019). We are now exploring the therapeutic potential of targeting this pathway in pancreatic cancer.
Sitting at this intersection of longitudinal care of hereditary pancreatic cancer families in the clinic, genome analysis, and zebrafish cancer models at the lab bench, our research group is well-positioned to continue making pivotal discoveries that will advance our understanding and management of pancreatic cancer.
Non-Zebrafish Publications
Most updated list:
https://www.ncbi.nlm.nih.gov/myncbi/1fC8hH7ueqf5f/bibliography/public/
Nissim S, Leshchiner I, Mancias JD, Greenblatt MB, Maertens O, Cassa CA, Rosenfeld JA, Cox AG, Hedgepeth J, Wucherpfennig JI, Kim AJ, Henderson JE, Gonyo P, Brandt A, Lorimer E, Unger B, Prokop JW, Heidel JR, Wang XX, Ukaegbu CI, Jennings BC, Paulo JA, Gableske S, Fierke CA, Getz G, Sunyaev SR, Wade Harper J, Cichowski K, Kimmelman AC, Houvras Y, Syngal S, Williams C, Goessling W. Mutations in RABL3 alter KRAS prenylation and are associated with hereditary pancreatic cancer. Nat Genet. 2019 Sep; 51(9):1308-1314. PMID: 31406347.
Cox AG, Tsomides A, Kim AJ, Saunders D, Hwang KL, Evason KJ, Heidel J, Brown KK, Yuan M, Lien EC, Lee BC, Nissim S, Dickinson B, Chhangawala S, Chang CJ, Asara JM, Houvras Y, Gladyshev VN, Goessling W. Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis. Proc Natl Acad Sci U S A. 2016 09 20; 113(38):E5562-71. PMID: 27588899.
Nissim S*, Weeks O*, Talbot JC, Hedgepeth JW, Wucherpfennig J, Schatzman-Bone S, Swinburne I, Cortes M, Alexa K, Megason S, North TE, Amacher SL, Goessling W. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development. Dev Biol. 2016 10 01; 418(1):108-123. PMID: 27474396.
Cox AG, Hwang KL, Brown KK, Evason K, Beltz S, Tsomides A, O'Connor K, Galli GG, Yimlamai D, Chhangawala S, Yuan M, Lien EC, Wucherpfennig J, Nissim S, Minami A, Cohen DE, Camargo FD, Asara JM, Houvras Y, Stainier DYR, Goessling W. Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth. Nat Cell Biol. 2016 08; 18(8):886-896. PMID: 27428308.
Mancias JD, Pontano Vaites L, Nissim S, Biancur DE, Kim AJ, Wang X, Liu Y, Goessling W, Kimmelman AC, Harper JW. Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis. Elife. 2015 Oct 05; 4. PMID: 26436293.
Esain V, Kwan W, Carroll KJ, Cortes M, Liu SY, Frechette GM, Sheward LM, Nissim S, Goessling W, North TE. Cannabinoid Receptor-2 Regulates Embryonic Hematopoietic Stem Cell Development via Prostaglandin E2 and P-Selectin Activity. Stem Cells. 2015 Aug; 33(8):2596-612. PMID: 25931248.
Carroll KJ, Esain V, Garnaas MK, Cortes M, Dovey MC, Nissim S, Frechette GM, Liu SY, Kwan W, Cutting CC, Harris JM, Gorelick DA, Halpern ME, Lawson ND, Goessling W, North TE. Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche. Dev Cell. 2014 May 27; 29(4):437-53. PMID: 24871948.
Nissim S, Sherwood RI, Wucherpfennig J, Saunders D, Harris JM, Esain V, Carroll KJ, Frechette GM, Kim AJ, Hwang KL, Cutting CC, Elledge S, North TE, Goessling W. Prostaglandin E2 regulates liver versus pancreas cell-fate decisions and endodermal outgrowth. Dev Cell. 2014 Feb 24; 28(4):423-37. PMID: 24530296.
Nissim S, Idos GE, Wu B. Genetic markers of malignant transformation in intraductal papillary mucinous neoplasm of the pancreas: a meta-analysis. Pancreas. 2012 Nov; 41(8):1195-205. PMID: 22750975.
Scherz PJ, McGlinn E, Nissim S, Tabin CJ. Extended exposure to Sonic hedgehog is required for patterning the posterior digits of the vertebrate limb. Dev Biol. 2007 Aug 15; 308(2):343-54. PMID: 17610861.
Nissim S, Allard P, Bandyopadhyay A, Harfe BD, Tabin CJ. Characterization of a novel ectodermal signaling center regulating Tbx2 and Shh in the vertebrate limb. Dev Biol. 2007 Apr 01; 304(1):9-21. PMID: 17300775.
Nissim S, Hasso SM, Fallon JF, Tabin CJ. Regulation of Gremlin expression in the posterior limb bud. Dev Biol. 2006 Nov 01; 299(1):12-21. PMID: 16989805.
Dentice M, Bandyopadhyay A, Gereben B, Callebaut I, Christoffolete MA, Kim BW, Nissim S, Mornon JP, Zavacki AM, Zeöld A, Capelo LP, Curcio-Morelli C, Ribeiro R, Harney JW, Tabin CJ, Bianco AC. The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate. Nat Cell Biol. 2005 Jul; 7(7):698-705. PMID: 15965468.
Harfe BD, Scherz PJ, Nissim S, Tian H, McMahon AP, Tabin CJ. Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identities. Cell. 2004 Aug 20; 118(4):517-28. PMID: 15315763.
Rallis C, Bruneau BG, Del Buono J, Seidman CE, Seidman JG, Nissim S, Tabin CJ, Logan MP. Tbx5 is required for forelimb bud formation and continued outgrowth. Development. 2003 Jun; 130(12):2741-51. PMID: 12736217.
Park KI, Lachyankar M, Nissim S, Snyder EY. Neural stem cells for CNS repair: state of the art and future directions. Adv Exp Med Biol. 2002; 506(Pt B):1291-6. PMID: 12614070.
Park KI, Liu S, Flax JD, Nissim S, Stieg PE, Snyder EY. Transplantation of neural progenitor and stem cells: developmental insights may suggest new therapies for spinal cord and other CNS dysfunction. J Neurotrauma. 1999 Aug; 16(8):675-87. PMID: 10511240.