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Dr. Mark Huising



Assistant Professor
Department of Neurobiology, Physiology & Behavior, College of Biological Sciences & Department of Physiology & Membrane Biology, School of Medicine
University of California, Davis

Hangout Topic: 'Urocortin3: How local crosstalk controls beta cell fate and function.’

Hangout Schedule: May 4th: 12pm EST, 11am CST, 9am PST, 9.30pm IST




Mark



 

Profile Introduction

ONE IN TWELVE AMERICANS suffers from diabetes. The incidence of diabetes will continue to increase with an estimated one in three adult Americans currently suffering from pre-diabetes and expected to develop frank diabetes in the foreseeable future. Type 2 diabetes (T2D), which occurs when the insulin-producing beta cells of the pancreas can no longer keep up with the increased demand for and decreased sensitivity to insulin, is the most prevalent form of the disease and is often associated with overweight or obesity. A smaller, but also rising number of around 1 million people in the US has Type 1 diabetes (T1D), which is driven by the progressive loss of the insulin-producing beta cells as a consequence of autoimmunity for which no cure exists. Despite all the advances of modern medicine and ever more sophisticated technology to monitor and control blood glucose, diabetes is still a major risk factor in the development of macro- and microvascular complications including cardiac failure and lower limb amputations. This illustrates the dire need for new therapies to combat, cure and prevent diabetes. We are at an important moment in time in diabetes research with the promise of stem cell derived beta cells, exciting new insight into the potential of beta cell neogenesis from a variety of endogenous precursors and the potential for target discovery through comprehensive interrogation of the epigenome and transcriptome by deep sequencing.

Websites

Degrees

2006 Ph.D. Comparative Neuroendocrinology and Immunology Radboud University Nijmegen, The Netherlands
2000 M.Sc. Biology Wageningen University, The Netherlands

Research Interests

Islet Biology and Diabetes, transcriptional control of beta cell differentiation and plasticity of pancreatic islet cell identity.

Proper control of glucose metabolism is essential to thrive. Consequently our bodies have evolved sophisticated and subtle yet remarkably effective ways to maintain tight blood glucose control over the course of many decades. Key to glucose homeostasis are the opposing actions of insulin, which promotes peripheral uptake of glucose, and glucagon, which is a signal to the liver to break down glycogen and release glucose. These hormones are made by beta and alpha cells, respectively, which co-localize in the islets of Langerhans to facilitate the coordinated regulation of their release. The islets also contain somatostatin-producing delta cells, which provide essential negative feedback to both alpha and beta cells. My group studies how the alpha, beta and delta cells within the islet communicate with each other and integrate signals from the central and peripheral nervous system, gastro-intestinal tract, liver, skeletal muscle and adipose tissue. We are only just starting to appreciate the depth and complexity of this intricate network, which contains potential therapeutic targets to treat or even cure diabetes.

 

One of the family of signals that the Huising lab studies, is named for the stress peptide Corticotropin Releasing Factor, or CRF in short. CRF was originally discovered as the principal hypothalamic factor to initiate the stress response by acting on the pituitary gland. It turns out that the insulin-producing beta cells of the pancreas can respond directly to CRF with increased insulin secretion, increased beta cell proliferation and reduced beta cell death in the face of pro-inflammatory insults, which is a promising set of beneficial characteristics united in a single molecule. Urocortin3 (Ucn3), a peptide related to CRF, is abundantly expressed by mature beta cells. We discovered that Ucn3 is co-released with insulin to trigger somatostatin release from neighboring delta cells, which in turn inhibits insulin secretion. In essence, Ucn3 triggers a negative feedback loop that attenuates insulin secretion, provided that glucose levels are successfully reduced. Ucn3 expression also distinguishes mature, functional beta cells from their immature progenitors, which is a trait that is particularly useful to track the differentiation of mature, glucose-responsive beta cells from embryonic or induced pluripotent stem cells. CRF and Ucn3 are just two examples of signaling molecules whose direct actions on the pancreas add a novel layer of complexity to the intricate network of signaling molecules that in concert governs beta cell mass and insulin and glucagon output of the pancreas. My group is focused on unraveling the contributions of these local pancreatic CRF family signaling cascades on glucose metabolism in healthy and diabetic individuals.

 

Awards

Dutch Zoology Award (2006) from the Royal Dutch Zoological Society
Endocrine Scholars Award (2007) from The Endocrine Society
Novo Nordisk Award for Endocrinology (2011) from the Dutch Endocrine Society
Career Development Award (2013) from the Juvenile Diabetes Research Foundation
Helmsley Award (2015) from the Endocrine Society and the Helmsley Charitable Trust
Individual Biomedical Research Award (2015) from the Hartwell Foundation
Nominated for the Helmholtz Young Investigator Diabetes Award (2016)

Department and Center Affiliations

Neurobiology, Physiology and Behavior
Physiology and Membrane Biology

ProfessionalSocieties

American Diabetes Association
The Endocrine Society
The American Association for the Advancement of Science

CBS Grad Group Affiliations

Molecular, Cellular, and Integrative Physiology
Biochemistry, Molecular, Cellular and Developmental Biology
Integrated Genetics and Genomics

Specialties / Focus

Biochemistry, Molecular, Cellular and Developmental Biology
  • Genomics, Proteomics and Metabolomics
  • Differentiation, Morphogenesis and Wound Healing
  • Developmental Biology
  • Gene Regulation
  • Molecular Physiology
  • Stem Cell Biology
Molecular, Cellular, and Integrative Physiology
  • Comparative Physiology
  • Endocrinology
  • Metabolic Physiology
  • Cellular Physiology
  • Molecular Physiology
  • Systemic Physiology

Labs

Huising Lab website
 

Publications