Photo of Sahar Nissim,  MD, PhD

Sahar Nissim, MD, PhD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 525-4716

Sahar Nissim, MD, PhD

Brigham And Women's Hospital


  • Assistant Professor, Medicine, Harvard Medical School
  • Associate Physician, Medicine, Brigham And Women's Hospital


Research Abstract

The Nissim Lab seeks to understand the signaling and epigenetic changes occurring in the earliest stages of cancer initiation in order to pioneer the first interception strategy for pancreatic cancer. Cancer interception seeks to actively interfere with the earliest events in cancer development in order to prevent progression to more heterogeneous and intractable disease. Effective interception strategies have yet to be identified for most cancers.

Towards this mission, our team leverages zebrafish and mouse models, developmental biology, gene discovery in hereditary cancer patient families seen at DFCI, and integrative transcriptomic, proteomic, and CUT&RUN technologies to answer these questions:

• What are the signaling and epigenetic processes that maintain normal cell identity?

How are these processes disrupted by cancer-initiating mutations?

And, can we reinforce the processes that maintain cell identity to counter pancreatic cancer formation?

• What are the causes of hereditary pancreatic cancer? Families with as many as five cases of pancreatic cancer are suspicious for a heritable etiology, but the genetic basis is not known in most families. While rare, these families offer precious insights into why pancreatic cancer forms. The DFCI Cancer Genetics clinic is an international referral center for such unsolved cancer families. Beginning with families encountered in Dr. Nissim’s clinic, the lab seeks to discover and characterize new causes of hereditary pancreatic cancer.

• GWAS have implicated pathways that modulate pancreatic cancer risk, but underlying mechanisms are not known. Can these pathways be targeted for pancreatic cancer prevention? In particular, the lab is studying the GWAS hit NR5A2, a nuclear receptor that can be pharmacologically targeted, as a potential target for pancreatic cancer prevention.

Dr. Sahar Nissim, MD, PhD, is a physician-scientist who trained at HMS, BWH, and DFCI. For more information about the lab, visit or email

Publications from Harvard Catalyst Profiles

Powered by Harvard Catalyst
  • Aney KJ, Nissim S. More than acinar identity? A novel cystic phenotype suggests broader roles for NR5A2 in pancreatic cancer. J Pathol 2021. PubMed
  • 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; 51:1308-1314. PubMed
  • 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; 418:108-23. PubMed
  • 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; 113:E5562-71. PubMed
  • Cox AG, Hwang KL, Brown KK, Evason KJ, 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 DY, Goessling W. Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth. Nat Cell Biol 2016; 18:886-96. PubMed
  • 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; 33:2596-612. PubMed
  • 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. PubMed
  • 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; 29:437-53. PubMed
  • 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; 28:423-37. PubMed
  • Nissim S, Idos GE, Wu B. Genetic markers of malignant transformation in intraductal papillary mucinous neoplasm of the pancreas: a meta-analysis. Pancreas 2012; 41:1195-205. PubMed
  • 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; 308:343-54. PubMed
  • 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; 304:9-21. PubMed
  • Nissim S, Hasso SM, Fallon JF, Tabin CJ. Regulation of Gremlin expression in the posterior limb bud. Dev Biol 2006; 299:12-21. PubMed
  • 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; 7:698-705. PubMed
  • 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; 118:517-28. PubMed
  • 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; 130:2741-51. PubMed
  • 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; 506:1291-6. PubMed