News from the UMass Diabetes Center of Excellence

This study conducted in the Brehm & Greiner labs and published in the The Journal of Leukocyte Biology describes the creation of a novel “humanized” mouse model that enables specific targeting of the human toll-like receptor 4 (TLR4) pathway in mice. These molecules help the immune system recognize infections and other harmful threats. Their new model allows scientists to test therapies in a human specific manner and show treatment efficacy against a human tumor.

Emilee Herringshaw is a UMass Chan Medical School student living with type 1 diabetes who is working towards a career in dermatology. She was awarded a clinical research grant by The American Contact Dermatitis Society to create a pilot study designed to evaluate skin reactions to continuous glucose monitors. Patients at the UMass Memorial Diabetes Center of Excellence are invited to participate and the data will be analyzed looking at all available devices, various scenarios & interventions.

The fourth annual Herman G. Berkman Diabetes Clinical Innovation Fund grant was awarded to optometrist Juan Ding, OD, PhD and co-investigator James Ledwith, MD, Department of Family Medicine and Community Health. Their project titled "Efficacy and Impact of Implementing an AI Diabetic Retinopathy Screening Program in Family Medicine Clinics" offers a path to identify eye disease and improve comprehensive care for people living with diabetes.

Brown adipose tissue (fat tissue) is known to burn fat and improve metabolism while and white adipose tissue stores fat. Scientists are exploring cellular and molecular mechanisms that control brown fat, and how to convert white adipocytes into brown-like adipocytes. A newly published study in Nature Communications led by Qingbo Chen, PhD, describes a brown fat-enriched adipokine they call Adissp (Adipose-secreted signaling protein) that is a key regulator for white adipose tissue thermogenesis and glucose homeostasis.

The Diabetes Center of Excellence at UMass Chan Medical School received a $250,000 donation from the Arthur M. and Martha R. Pappas Foundation.  The funds were used to purchase and maintain a state-of-the-art flow cytometer to characterize cells and their functional and signaling properties.  It provides quantitative data on immune cell and pancreatic islet cell phenotypes to facilitate the analysis of samples and greatly expand our research team’s capacity to rapidly screen experimental samples. 
FULL STORY & VIDEO ABOUT DR. ARTHUR PAPPAS

Viral infections continue to be linked to the development of type 1 diabetes, yet human immune responses to viruses and how that leads to the destruction of insulin-producing beta cells in the pancreas is still unknown.  The laboratory of Jennifer Wang, MD, investigated inflammatory pathways because viruses can trigger inflammation that damages the pancreas.  The research focused on early events leading to autoimmune responses to viruses with the ultimate goal of therapeutics that could target inflammation before T1D manifests.

Teplizumab (Tzield) was approved by the U.S. Food and Drug Administration to delay the onset of type 1 diabetes when identified in the pre-symptomatic stage. A statement was released by the UMass Memorial Diabetes Center of Excellence regarding the new medication.

The 5th for Worcester’s homeless population was a multidisciplinary outreach event with providers from the Diabetes Center of Excellence, vascular surgery, podiatry & more. They volunteered to examine people, provided information & resources and scheduled follow-up appointments if needed. PHOTOS

The Joseph “Nuzzy” Nozzolillo Memorial Foundation added a $25K donation in 2022 to their ongoing support of the UMass Diabetes Center of Excellence, raising their five-year fundraising total to $85,560. The 5th annual Nuzzy Memorial Golf Tournament and third “Rockin’ for Nuzzy” fundraiser concert were held by Joe's family and friends who are grateful for the care he received and optimistic about the diabetes research taking place at the UMass Chan DCOE.  PHOTOS & VIDEO

A five-year grant from the NIH/NIAMS was awarded to John Harris, MD, PhD, Founding Director of the Vitiligo Clinic & Research Center, and Autoimmune Therapeutics Institute at UMass Chan Medical School. The project is entitled Dissecting Functional Autoimmunity through High-Resolution Multiomics in a Vitiligo Center of Research Translation. Dr. Kent is leading Project 1, Autoreactive T Cell Function in Vitiligo.

The Czech lab examined the metabolic regulation of adipocytes by insulin receptor signaling and the cAMP signaling pathway in a review article published in the journal Trends in Cell Biology. The two major signaling networks regulate virtually every organ and/or cell type in the human body.  While the two signaling pathways intercommunicate regularly in fat cells, published data has shown they typically counteract one other in most cellular processes. Their opposite roles are indispensable for adipocyte physiology and metabolic homeostasis. Together they constitute what the Czech lab calls “the adipocyte supersystem.” However, their review highlights a set of genes that are known to promote metabolic health and were activated by both insulin and catecholamines in the same way.  

Sally Kent, PhD was awarded a Multi-Principal Investigator grant from the NIH/NIDDK entitled Extracellular Vesicle-mediated islet immune cross talk in type 1 diabetes pathogenesis. The project will examine the function of extracellular vesicles originating directly from pancreatic islets in people with  type 1 diabetes. The goal of these studies is to understand their functional role in the autoimmune process and to provide biomarkers for disease development.

Dr. O’Connor was co-recipient of the UMass Memorial Medical Group’s Prize for Academic Collaboration and Excellence (PACE) Award. It supports physicians in cutting-edge research and encourages interdepartmental collaboration. His project is studying the benefits of using widely available wearable devices such as smart watches, to protect people who are living with diabetes, from dangerous hypoglycemia. A pilot study of people with type 1 diabetes who are at risk for hypoglycemia will create an optimized algorithm for detecting hypoglycemia based on smart watch data.

The study aims to generate CAR T cell variants that would target and eliminate islet specific autoreactive T cells in people with type 1 diabetes. A grant from the NIH/NIDDK with Multi-Principal Investigators was awarded to investigate CAR T-cell technology as a potential T1D therapy. 

In a newly published study in the FASEB journal, the laboratories of Michael Brehm, PhD and Dale Greiner, PhD describe a novel humanized mouse model developed with improved Natural Killer (NK) cell acceptance and functionality.  Their data explains the potential for this in vivo model to study human NK cell biology and to test new human-specific immune-therapies that target NK cells. 

Vascular surgeon-scientist Tammy Nguyen, MD, PhD, is the recipient of a K08 Clinical Investigator Award from the National Institute of Diabetes and Digestive and Kidney Diseases to advance her independent clinical research. Dr. Nguyen wants to understand why people with diabetes have a difficult time with wound healing, particularly foot ulcers. She’s studying the effect of type 2 diabetes on the development of the immune system, with the goal of designing targeted therapies to combat poor wound healing. As the Medical Director of the Lower Extremity Wound Clinic at UMass Memorial Health, she continues to perform surgeries on people with diabetes who developed uncontrolled infections that led to amputations. 

A significant percentage of people living with type 2 diabetes also have too much fat accumulated in their liver that can develop into a condition called nonalcoholic steatohepatitis (NASH). It’s characterized by severe liver inflammation and fibrosis that can lead to cirrhosis and may require a liver transplantation. Currently, there is no medication for NASH. To better understand how a medicine might be developed, the Czech lab studied fat production in the liver from carbohydrates by disrupting an enzyme that helps to convert blood glucose into fat in obese mice. Results of their research is published in the Journal of Biological Chemistry.

Meet Clinical Research Assistant Lucy Ding and learn about two studies she's involved with that are designed to help hospitalized patients living with diabetes.  One is a randomized clinical trial that provides continuous glucose monitors to people with diabetes who are currently not using one and arrive at the Emergency Room with high or low blood sugar, or other diabetes related complications. The other study is implementing a carbohydrate counting system for hospitalized inpatients with diabetes throughout the UMass Memorial Health system.

The laboratory of Jason Kim, PhD welcomes two visiting professors from Kosin University College of Medicine in South Korea. Both physician-scientists will be conducting diabetes research at UMass Chan Medical School through 2023.  

Dr. Kim’s daughters Allison and Lauren are also considering careers in medicine and science. When Lauren’s 2020 summer research internship at Harvard Medical School was canceled due to the COVID-19 pandemic, the family quickly created the Diabetes Virtual Camp to connect students and experts in a virtual internship setting.  

Dr. David Harlan has been named the new director of the JDRF Center of Excellence in New England. For nearly 40 years, Dr. Harlan has been conducting research exploring the pathophysiology underlying diabetes. He also brings years of experience as an endocrinologist with expertise in diabetes and metabolism. A renowned basic and clinical investigator, his current research is focused on beta cell biology and the anti-beta cell immune response. The Center is genetically modifying beta cells with the goal of making them invulnerable to the immune system when infused as a therapy into a person with type 1 diabetes.

Tammy Nguyen, MD, PhD is a vascular surgeon-scientist who is interested in understanding why people living with diabetes have trouble getting foot wounds to heal. This career development grant will provide $150,000 over the next three years for her project “Exploring How the Diabetic Immune System Contributes to Non-Healing Ulcers.” Dr. Nguyen is studying the effect of type 2 diabetes (T2D) on the development of the immune system to design targeted therapies to combat poor wound healing for people with T2D. She developed a novel method to collect and expand human stem cells directly from the bone marrow of donors both with and without T2D who underwent lower extremity amputation for non-healing wounds.

Despite attending an American Diabetes Association-recognized education program at the UMass Memorial Health Diabetes Center of Excellence (DCOE), some people still struggle to keep their blood glucose within a healthy range. The DCOE piloted a Care Coach Program in collaboration with Shields Health Care Group to provide supplemental support to help them manage blood glucose levels. Participants have successfully lowered their A1c and demonstrated a reduction in the distress caused by their diabetes by implementing behavioral, lifestyle, and medication changes, thanks to more frequent contact with a diabetes expert to administer the care plan developed by their endocrinologist and/or nurse practitioner.  

Endocrinologist Mark O'Connor, MD, led the largest genome-wide meta-analysis study ever done using a recessive model for Type 2 diabetes.  It identified 51 loci associated with diabetes, including five that were undetected by past additive analyses.  The results were published in the journal Diabetes demonstrating that recessive models can identify new genetic risk factors for T2D, including variants with large effect sizes.  

The Czech Lab is using genetic engineering to investigate a therapeutic approach to Type 2 diabetes.  Senior scientist Sarah Nicoloro's research involves the modification of genes of adipocytes to increase fat burning and improve their metabolic function as a potential therapy.  When she joined the lab in 1998, their focus was to learn about the interactions taking place within adipocytes, particularly insulin signaling and GLUT4 trafficking. She was part of a team of scientists who developed a novel small interfering RNA (siRNA) delivery system. Learn more about Sarah and her research.