Dipak Panigrahy, MD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2400


dipak.panigrahy@childrens.harvard.edu

Dipak Panigrahy, MD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Pathology, Harvard Medical School
  • Instructor in Surgery, Vascular Biology Program, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Inflammatory processes in the tumor stroma are increasingly implicated in tumorigenesis and associated angiogenesis. While most effort to elucidate the mediators involved focus on cytokines, the role of non-proteinaceous autacoids have received little attention. We recently discovered that the eicosanoids such as epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid (AA), have potent tumor promoting activities. Overexpression of the CYP enzymes (which convert AA to EETs) or genetic abrogation of the enzyme sEH (which metabolizes EETs) were used to increase EET levels in transgenic mice. In both cases increased EETs dramatically stimulated angiogenesis, tumor growth, and metastasis. Consistently, reducing endogenous EETs using specific EET-antagonists or through endothelial-specific overexpression of sEH inhibited tumor growth. Thus, we hypothesize that EET in endothelium is a potent regulator of tumor growth and metastasis. Eicosanoids such as EETs may thus be a key paracrine mediator of the tumor promoting role of inflammation. The overall goal of the Panigrahy laboratory is thus is to elucidate the mechanisms by which eicosanoids such as EETs can stimulate tumor growth. Understanding the role of eicosanoids in tumorigenesis is of direct clinical relevance as the pharmacologically accessible autacoids system, such as EETs, may offer an entirely new system of targets for anti-stromal and anti-angiogenesis strategies in cancer therapy.

 

Publications

Powered by Harvard Catalyst
  • Panigrahy D, Adini I, Mamluk R, Levonyak N, Bruns CJ, D'Amore PA, Klagsbrun M, Bielenberg DR. Regulation of soluble neuropilin 1, an endogenous angiogenesis inhibitor, in liver development and regeneration. Pathology 2014; 46:416-23. PubMed
  • Zhang G, Panigrahy D, Hwang SH, Yang J, Mahakian LM, Wettersten HI, Liu JY, Wang Y, Ingham ES, Tam S, Kieran MW, Weiss RH, Ferrara KW, Hammock BD. Dual inhibition of cyclooxygenase-2 and soluble epoxide hydrolase synergistically suppresses primary tumor growth and metastasis. Proc Natl Acad Sci U S A 2014; 111:11127-32. PubMed
  • Wang W, Zhu J, Lyu F, Panigrahy D, Ferrara KW, Hammock B, Zhang G. ω-3 Polyunsaturated fatty acids-derived lipid metabolites on angiogenesis, inflammation and cancer. 2014. PubMed
  • Dahlman JE, Barnes C, Khan O, Thiriot A, Jhunjunwala S, Shaw TE, Xing Y, Sager HB, Sahay G, Speciner L, Bader A, Bogorad RL, Yin H, Racie T, Dong Y, Jiang S, Seedorf D, Dave A, Sandu KS, Webber MJ, Novobrantseva T, Ruda VM, Lytton-Jean AK, Levins CG, Kalish B, Mudge DK, Perez M, Abezgauz L, Dutta P, Smith L, Charisse K, Kieran MW, Fitzgerald K, Nahrendorf M, Danino D, Tuder RM, von Andrian UH, Akinc A, Panigrahy D, Schroeder A, Kotelianski V, Langer R, Anderson DG. In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight. Nat Nanotechnol 2014. PubMed
  • Mammoto T, Jiang A, Jiang E, Panigrahy D, Kieran MW, Mammoto A. Role of collagen matrix in tumor angiogenesis and glioblastoma multiforme progression. Am J Pathol 2013; 183:1293-305. PubMed
  • Panigrahy D, Kalish BT, Huang S, Bielenberg DR, Le HD, Yang J, Edin ML, Lee CR, Benny O, Mudge DK, Butterfield CE, Mammoto A, Mammoto T, Inceoglu B, Jenkins RL, Simpson MA, Akino T, Lih FB, Tomer KB, Ingber DE, Hammock BD, Falck JR, Manthati VL, Kaipainen A, D'Amore PA, Puder M, Zeldin DC, Kieran MW. Epoxyeicosanoids promote organ and tissue regeneration. Proc Natl Acad Sci U S A 2013; 110:13528-33. PubMed
  • Dearling JL, Barnes JW, Panigrahy D, Zimmerman RE, Fahey F, Treves ST, Morrison MS, Kieran MW, Packard AB. Specific uptake of 99mTc-NC100692, an 留v硫3-targeted imaging probe, in subcutaneous and orthotopic tumors. Nucl Med Biol 2013; 40:788-94. PubMed
  • Zhang G, Panigrahy D, Mahakian LM, Yang J, Liu JY, Stephen Lee KS, Wettersten HI, Ulu A, Hu X, Tam S, Hwang SH, Ingham ES, Kieran MW, Weiss RH, Ferrara KW, Hammock BD. Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis. Proc Natl Acad Sci U S A 2013; 110:6530-5. PubMed
  • Stahl A, Joyal JS, Chen J, Sapieha P, Juan AM, Hatton CJ, Pei DT, Hurst CG, Seaward MR, Krah NM, Dennison RJ, Greene ER, Boscolo E, Panigrahy D, Smith LE. SOCS3 is an endogenous inhibitor of pathologic angiogenesis. Blood 2012; 120:2925-9. PubMed
  • Fernandez CA, Roy R, Lee S, Yang J, Panigrahy D, Van Vliet KJ, Moses MA. The anti-angiogenic peptide, Loop 6, binds IGF-IR. J Biol Chem 2010; 285:41886-95. PubMed
  • Panigrahy D, Kaipainen A, Greene ER, Huang S. Cytochrome P450-derived eicosanoids: the neglected pathway in cancer. Cancer Metastasis Rev 2010; 29:723-35. PubMed
  • Benny O, Nakai K, Yoshimura T, Bazinet L, Akula JD, Nakao S, Hafezi-Moghadam A, Panigrahy D, Pakneshan P, D'Amato RJ. Broad spectrum antiangiogenic treatment for ocular neovascular diseases. PLoS ONE 2010. PubMed
  • Robbins ME, Linard C, Panigrahy D. PPARs and Anticancer Therapies. PPAR Res 2010; 2010:536415. PubMed
  • Kalish BT, Kieran MW, Puder M, Panigrahy D. The growing role of eicosanoids in tissue regeneration, repair, and wound healing. 2013; 104-105:130-8. PubMed
  • Panigrahy D, Kaipainen A, Huang S, Butterfield CE, Barnes CM, Fannon M, Laforme AM, Chaponis DM, Folkman, J, Kieran MW . PPARalpha ligand fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition Proc Natl Acad Sci U S A 2006.
Hide