Amnon Schlegel

Amnon Schlegel, MD, PhD

Languages spoken: English

Academic Information

Departments Adjunct - Biochemistry

Lab

Board Certification

  • American Board of Internal Medicine (Sub: Endocrinology, Diabetes & Metabolism)

Research Interests

  • Adipose Tissue
  • Biochemistry
  • Diabetes Mellitus
  • Endocrinology
  • Hormones
  • Lipids
  • Molecular Genetics
  • Obesity
  • Kinase
  • Zebrafish
  • Non-alcoholic Fatty Liver Disease
  • Monocarboxylate Transporter
  • Ketone Bodies

Dr. Schlegel is a board certified specialist in Adult Endocrinology, Metabolism and Diabetes.

Research Statement

For the first decade of its operation, my laboratory took a multi-pronged approach to identifying and characterizing novel genes involved in lipid and glucose metabolism. We now focus on the most promising leads from this search—fasting processes that contribute to the development of type 2 diabetes mellitus—in the hopes of developing better diagnostic and therapeutic modalities to treat this pandemic, multi-organ illness. The central area of study is how the transcriptional repressor FOXN3, whose gene locus is associated with fasting blood glucose in population genetic studies, acts to regulate metabolism. FOXN3 is silenced in a wide array of cancers via uniqee mechanisms (e.g., intron polyadenylation, targeted pre-mRNA decay), and I am establishing several mouse cancer models where FOXN3 is absent. A second major area is the study of the ketone body transporter SLC16A6, whose encoding gene is amplified in several cancers. This work spans human physiology, genetically engineered mice and zebrafish, and cell-based approaches. Other areas of interest over my career included intestinal lipid transport and development of novel insulins based on cone snail venom insulin. I am also interested in monogenetic diabetes and dyslipidemia syndromes, areas that interface directly with areas of interest in clinical effort.

Education History

Fellowship University of California, San Francisco
 Fellow
Beth Israel Deaconess Medical Center
 Resident
Internship Beth Israel Deaconess Medical Center
 Intern
Albert Einstein College of Medicine
 PhD
Graduate Training Albert Einstein College of Medicine
 MS
Albert Einstein College of Medicine
 MD
Undergraduate Hofstra University
 BS

Selected Publications

Journal Article

  1. Wang M-Y, Dean ED, Quittner-Strom E, Zhu Y, Chowdhury KH, Zhang Z, Zhao S, Li N, Ye R, Lee Y, Zhang Y, Chen S, Yu X, Leonard DC, Poffenberger G, Von Dylen A, McCorkle SK, Schlegel A, Sloop KW, Efanov AM, Gimeno RE, Scherer PE, Powers AC, Unger RH, Holland WL (2021). Glucagon blockade restores functional β-cell mass in type 1 diabetic mice and enhances function of human islets. Proc Natl Acad Sci U S A, 118(9), e2022142118.
  2. Karanth S, Chaurasia B, Bowman FM, Tippets TS, Holland WL, Summers SA, Schlegel A (2019). FOXN3 controls liver glucose mentalism by regulating gluconeogenic substrate selection. Physiol Rep, 7(18), e14238.
  3. Erickson ML, Karanth S, Ravussin E, Schlegel A (2019). FOXN3 hyperglycemic risk allele and insulin sensitivity in humans. BMJ Open Diabetes Res Care, 7(1), e000688.
  4. Karanth S, Adams JD, Serrano MLA, Quittner-Strom E, Simcox J, Villanueva CJ, Ozcan L, Holland WL, Yost HJ, Vella A, Schlegel A (2018). A hepatocyte FOXN3—α cell glucagon alpha-axis regulates fasting glucose. Cell Rep, 24(2), 312-319.
  5. Hugo SE, Schlegel A (2017). A genetic model to study increased hexosamine biosynthetic flux. Endocrinology, 158(8), 2420-2426.
  6. Benitez-Santana T, Hugo SE, Schlegel A (2017). Role of intestinal LXRα in regulating post-prandial lipid excursion and diet-induced hypercholesterolemia and hepatic lipid accumulation. Front Physiol, 8, 280.
  7. Hugo SE, Schlegel A (2017). A genetic screen for zebrafish mutants with hepatic steatosis identifies a locus required for larval growth. J Anat, 230(3), 407-413.
  8. Karanth S, Zinkhan EK, Hill JT, Yost HJ, Schlegel A (2016). FOXN3 regulates hepatic glucose utilization. Cell Rep, 15(12), 2745-2755.
  9. Cruz-Garcia L, Schlegel A (2014). Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids. J Lipid Res, 55(9), 1944-1958.
  10. Karanth S, Tran VM, Kuberan B, Schlegel A (2013). Polyunsaturated fatty acyl-Coenzyme As are inhibitors of cholesterol biosynthesis in zebrafish and mice. Dis Model Mech, 6(6), 1365-1377.
  11. Hugo SE, Cruz-Garcia L, Karanth S, Anderson RM, Stainier DYR, Schlegel A (2012). A monocarboxylate transporter required for hepatocyte secretion of ketone bodies during fasting. Genes Dev, 26(3), 282-293.

Review

  1. Schlegel A (2016). Zebrafish models for dyslipidemia and atherosclerosis research. [Review]. Front Endocrinol (Lausanne), 7, 159.
  2. Schlegel A, Gut P (2015). Metabolic Insights from Zebrafish Genetics, Physiology, and Chemical Biology. [Review]. Cell Mol Life Sci, 72(12), 2249-2260.
  3. Schlegel, A (2012). Studying nonalcoholic fatty liver disease with zebrafish-- a confluence of optics, genetics, and physiology. [Review]. Cell Mol Life Sci, 69(23), 3965-3961.

Case Report

  1. Schlegel A (2024). Diagnostic challenge of an APOB variant of uncertain significance resolved by transheterozygosity with a pathological LDLR variant and clinical response to therapy. Atherosclerosis, 26, 117460.
  2. Schlegel A, Petersen WC, Holbrook AA, Iverson LK, Graham TE (2022). A novel INS mutation in the C-peptide region causing hyperproinsulinemic maturity onset diabetes of youth type 10. Lab Med, Online ahead of print.
  3. Schlegel A (2022). Macroprolactinoma-induced syndrome of inappropriate antidiuresis and its reversal with dopamine agonist therapy. Lab Med, 53(5), 537-539.
  4. Schlegel A (2022). Identifying glucocorticoid insufficiency in silent corticotroph adenoma with elevated adrenocorticotropic hormone  . Lab Med, 53(1), 91-94.
  5. Rios M, Wahl MP, Simmons DL, Schlegel A (2020). Skull base lymphoma with panhypopituitarism. Lancet Oncol, 21(8), 55.

Patent

  1. Safavi-Hemami H, Olivera BM, Gajewiak J, Karanth S, Schlegel A, Bandyopadhyay P, Yandell M, Robinson S (2016). Insulin analogs having shortened b chain peptides and associated methods. WO 2016172269 A3. U.S. Patent No. WO 2016172269 A3. Washington, D.C.:U.S. Patent and Trademark Office.