Joseph Pisegna, MD

Molecular genetics and physiology laboratory

Key investigators

  • Joseph Pisegna, MD
  • Patrizia M. Germano, MD
  • Suwan Oh, PhD

Funding

  • Department of Veterans Affairs Project Number: I01BX006367-01A2; Title: BCCMA: VA Colorectal Cancer Clinical & Computational Collaborative (VA-5C); Role: PI/PD; 07/01/2025 to 06/30/2029
  • Department of Veterans Affairs; BCCMA: Targeting Gut Microbiome in Gastrointestinal and Liver Diseases in US Veterans; CMA4: At the Crossroads of Gut Microbiome, Cirrhosis, and PTSD. I01CX002472; Co-PI (Bajaj PD/PI)
  • NIH/NIDDK 1U01DK127403-01 (Godarzi, PI); Title: Southern California Clinical Center of the Type 1 Diabetes in Acute Pancreatitis Consortium; 12/1/2020-11/30/2025
  • NCI 1R01CA260955-01 (Li,PI); Title: Intelligence Methods for Computed Tomography Early Detection of Pancreatic Cancer; 12/1/2021-11/30/2026
  • NIDDK/NCI U01DK108314 (PI-Pandol/Goodarzi); Greater Los Angeles Clinical Center of the Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer; 10/01/2022 – 09/30/2026
  • Department of Defense Peer Reviewed Medical Research Program (PRMRP); Title: A Case-CrossovEr Study deSign to inform tailored interventions for Alcoholic Pancreatitis (ACCESS-AP); Role: Co-I PR182623 (Jeon, PI); 09/15/2019 - 09/14/2023 (NCE)
  • Department of Veterans Affairs Cooperative Study Program CSP 577 Confirm Trial (PI,Dominitz); 10/01/2012-09/30/2020
  • Department of Veterans Affairs CSP 2023 Premium Study (LSI Pisegna); 10/1/2023-9/30/2029

Current research projects

  • Evaluation of the role of high protein dietary intervention in metabolic syndrome
  • Evaluation of the role of high protein dietary intervention in hepatic steatosis
  • Role of PACAP in metabolic syndrome
  • Role of PACAP and VIP in mouse models of colitis
  • Role of VIP in metabolic syndrome and hepatic steatosis
  • GWAS studies in colonic polyps, NAFLD and NASH
  • Pathophysiology, epidemiology and prevention of pancreatogenic diabetes
  • Pathophysiology of gastrin and VIP on the regulation of gastric and renal function

Future research directions

  • Genetic basis for metabolic syndrome, NAFLD and NASH
  • Pathophysiological basis for hormone and receptors to regulate gastrointestinal function
  • Neuroendocrine tumor-pathophysiology and genetic basis
  • Gastrointestinal regulation of renal physiologic function

Key publications - Full list on PubMed

  1. Rao S, Yang X, Ohshiro K, Zaidi S, Wang Z, Shetty K, Xiang X, Hassan I, Mohammad T, Latham PS, Nguyen BN, Wong L, Yu H, Al-Abed Y, Mishra B, Vacca M, Guenigault G, Allison MED, Vidal-Puig A, Benhammou JN, Alvarez M, Pajukanta P, Pisegna JR, Mishra L. β2-spectrin (SPTBN1) as a therapeutic target for diet-induced liver disease and preventing cancer development. Sci Transl Med. 2021 Dec 15;13(624):eabk2267.doi: 10.1126/scitranslmed.abk2267
  2. Van C, Condro MC, Lov K, Zhu R, Ricaflanca PT, Ko HH, Diep AL, Hoang AQ, Pisegna J, Rohrer H, Waschek JA. PACAP/PAC1 Regulation of Inflammation via the Sympathetic Nervous System in a Model of Multiple Sclerosis. J Mol Neurosci. 2018 Jul 30. doi: 10.1007/s12031-018-1137-8. PMID:30058008
  3. Jacobs JP, Dong TS, Agopian V, Lagishetty V, Sundaram V, Noureddin M, Ayoub WS, Durazo F, Benhammou J, Enayati P, Elashoff D, Goodman MT, Pisegna J, Hussain S. Microbiome and bile acid profiles in duodenal aspirates from patients with liver cirrhosis: The Microbiome, Microbial Markers and Liver Disease Study. Hepatol Res. 2018 Jun 20. doi: 10.1111/hepr.13207. PMID:29923681
  4. Mohapatra SS, Batra SK, Bharadwaj S, Bouvet M, Cosman B, Goel A, Jogunoori W, Kelley MJ, Mishra L, Mishra B, Mohapatra S, Patel B, Pisegna JR, Raufman JP, Rao S, Roy H, Scheuner M, Singh S, Vidyarthi G, White J. Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions. Dig Dis Sci. 2018 May;63(5):1123-1138. doi: 10.1007/s10620-018-5000-0. Epub 2018 Mar 23. Review.PMID:29572615
  5. Benhammou JN, Dong TS, May FP, Kawamoto J, Dixit R, Jackson S, Dixit V, Bhattacharya D, Han SB, Pisegna JR. Race affects SVR12 in a large and ethnically diverse hepatitis C-infected patient population following treatment with direct-acting antivirals: Analysis of a single-center Department of Veterans Affairs cohort. Pharmacol Res Perspect. 2018 Feb 22;6(2):e00379. doi: 10.1002/prp2.379. 2018 Apr.
  6. Ehrlich D, Jamaluddin N, Pisegna J, Padua D. A Challenging Case of Severe Ulcerative Colitis following the Initiation of Secukinumab for Ankylosing Spondylitis. Case Rep Gastrointest Med. 2018 Feb 15;2018:9679287. PMID:29666723
  7. Vu JP, Luong L, Parsons WF, Oh S, Sanford D, Gabalski A, Lighton JR, Pisegna JR, Germano PM. Long-Term Intake of a High-Protein Diet Affects Body Phenotype, Metabolism, and Plasma Hormones in Mice. J Nutr. 2017 Dec;147(12):2243-2251. doi: 10.3945/jn.117.257873. Epub 2017 Oct 25.PMID:29070713
  8. Aby ES, Dong TS, Kawamoto J, Pisegna JR, Benhammou JN. Impact of sustained virologic response on chronic kidney disease progression in hepatitis C. World J Hepatol. 2017 Dec 28;9(36):1352-1360. doi: 10.4254/wjh.v9.i36.1352.PMID: 29359019
  9. Wang L, Jacobs JP, Lagishetty V, Yuan PQ, Million M, Reeve JR, Pisegna J and Tache Y High protein diet promotes sensitity to cholecystokinin and shifts the cecal microbiome without altering brain inflammation in diet induced obesity in rats. Am J Physiol Regul Integr Comp Physiol 2017 Jul 19.
  10. Calais J, Czernin J, Eiber M, Fendler WP, Gartmann J, Heaney A, Hendifar A, Pisegna J, Hecht JR, Wolin E, Slavik R, Gupta P, Quon A, Schiepers C, Allen-Auerbach M, Herrmann K. Most Intended Management Changes after 68-Ga-DOTATATE PET/CT are Implemented J Nucl Med. 2017 May 4. pii: jnumed.117.192450. doi: 10.2967/jnumed.117.192450. PMID:28473600
  11. Li R, Yang J, Saffari A, Jacobs J, Baek KI, Hough G, Larauche MH, Ma J, Jen N, Moussaoui N, Zhou B, Kang H, Reddy S, Henning SM, Campen MJ, Pisegna J, Li Z, Fogelman AM, Sioutas C, Navab M, Hsiai TK. Ambient Ultrafine Particle Ingestion Alters Gut Microbiota in Association with Increased Atherogenic Lipid Metabolites. Sci Rep. 2017 Feb 17;7:42906. PMID: 28211537
  12. Benhammou JN, Phan J, Lee H, Ghassemi K, Parsons W, Grody WW, Pisegna JR. A Sodium Channel Myotonia Presenting with Intermittent Dysphagia as a Manifestation of a Rare SCN4A Variant. J Mol Neurosci. 2016 Dec 23. doi: 10.1007/s12031-016-0878-5.PMID:28012096.
  13. Padua D, Mahurkar-Joshi S, Law I, Polytarchou C, Vu J, Pisegna J, Shih D, Iliopolous D, and Pothoulakis C A Long noncoding RNA signature for ulcerative colitis identifies IFNG-AS1 as an enhancer of inflammation. American Journal of Physiology 2016 311(3):G446-57.
  14. Wang J, Benhammou JN, Ghassemi K, Kim S, Pisegna JR (2017) Endoscopic Ultrasound-Guided Fine Needle Aspiration Accurately Diagnoses Smaller Pancreatic Neuroendocrine Tumors Compared To Computer Tomography-Guided Fine Needle Aspiration. Gastroenterol Pancreatol Liver Disord 4(2): 1-7.
  15. Padua D, Vu JP, Germano PM, Pisegna JR. The Role of Neuropeptides in Mouse Models of Colitis. J Mol Neurosci. 2016 Jun;59(2):203-10. doi: 10.1007/s12031-015-0688-1. Epub 2015 Dec 8. Review.PMID:26646243
  16. Vu JP, Goyal D, Luong L, Oh S, Sandhu R, Norris J, Parsons W, Pisegna JR, Germano P. PACAP intraperitoneal treatment suppresses appetite and food intake via PAC1 receptor in mice, by inhibiting ghrelin and increasing GLP-1 and leptin. Am J Physiol Gastrointest Liver Physiol. 2015 Sep 3:ajpgi.00190.2015. doi: 10.1152/ajpgi.00190.2015. [Epub ahead of print]
  17. Vu JP, Larauche M, Flores M, Luong L, Norris J, Oh S, Liang LJ, Waschek J, Pisegna JR, Germano PM. Regulation of Appetite, Body Composition, and Metabolic Hormones by Vasoactive Intestinal Polypeptide (VIP). J Mol Neurosci. 2015 Jun;56(2):377-87.
  18. Vu JP, Million M, Larauche M, Luong L, Norris J, Waschek JA, Pothoulakis C, Pisegna JR, Germano PM. Inhibition of vasoactive intestinal polypeptide (VIP) induces resistance to dextran sodium sulfate (DSS)-induced colitis in mice. J Mol Neurosci. 2014 Jan;52(1):37-47.

Past GI research fellows

  • Joon Ki Choi, MD
  • Jihane N. Benhammou, MD, PhD
  • Tien S. Dong, MD, PhD
  • Arpana Church, PhD
  • Deepinder Goyal, MD
  • Noam Jacobs, MD, PhD
  • Sang Le, MD
  • Edward Lee, MD, MS
  • Edward Lew, MD, MS
  • Elizabeth Marcus, MD
  • Rong-Ming Lyu, PhD
  • Hank Wang, MD, MS
  • Emily Whang, MD
  • Ning Zeng, MD, PhD

About Dr. Pisegna

Dr. Pisegna is the chief of the Division of Gastroenterology, Hepatology and Parenteral Nutrition at the Veterans Administration Greater Los Angeles Healthcare System, Wadsworth VA and a professor of medicine and human genetics in the David Geffen School of Medicine at UCLA. Dr. Pisegna’s main research interest is the molecular pharmacology of hormones and their receptors in the gastrointestinal tract. These research and clinical interests derive from research in the biochemistry and molecular physiology of neuroendocrine tumors as well as an understanding of the molecular interaction of peptide hormones and their receptors. His clinical efforts are currently focused on the management of gastric hypersecretory conditions, neuroendocrine tumors of the GI tract and Zollinger Ellison Syndrome (ZES), medical conditions that derive from alterations in the expression of gastrointestinal hormones. Dr. Pisegna cloned the receptor for human cholecystokinin A (CCKA), the cholecystokinin B (CCKB or gastrin) receptor and the pituitary adenylate cyclase activating polypeptide (PACAP) receptor. He has previously demonstrated that PACAP is a potent stimulant of gastric acid secretion and is expressed on neurons innervating the stomach, on enterochromaffin-like cells (ECL) of the stomach expressing receptors for PACAP. Using mice lacking the PAC1 receptor, he has demonstrated that the mice develop a gastric acid hypersecretory condition resulting from hypergastrinemia. In addition, these mice also develop obesity and fatty liver. Dr. Pisegna has shown that PACAP can reverse the effects of obesity and fatty liver and has recently patented a peptide, MAXCAP that is undergoing preclinical studies as a treatment of obesity and fatty liver. Dr. Pisegna's research interests extend to understanding the molecular mechanisms involved in satiety and metabolic syndrome including the role of the gastrointestinal microbiome in malignancy. He was recently awarded a Department of Veterans Affairs Merit Review grant to investigate the microbiome and transcriptome of colorectal polyps and cancer. He is also funded to investigate the pathogenesis of pancreatic cancer and pancreatitis through grants from the Department of Defense and National Cancer Institute.