Remedi Lab

The major focus of the Remedi laboratory is to study in vivo physiology in various mouse models of diabetes to unravel the underlying mechanisms of pancreatic β-cell failure in glucotoxic stages, and their consequences in both pancreatic and extra-pancreatic tissues. Development of secondary loss of β-cell mass and antidiabetic drug sensitivity in long-standing diabetic patients is not completely understood. Recently, much attention has been gathered on cell plasticity challenging the current paradigms of how diabetes progresses.

Remedi Lab 2021
Research

The Bionic Mouse

Mice lacking the glycolytic enzyme glucokinase in the pancreas normally never live beyond a few days. The white mouse in the picture lacks glucokinase, but also lacks potassium channels. For this reason it bypasses the need for glucose metabolism in insulin secretion. It remains small and unhealthy but -critically- it can survive (Remedi et al. 2005 Diabetes 54, 2925–2931).


Neonatal Diabetes Mellitus is Genetic and Inherited

A genetically modified mouse model of Neonatal Diabetes Mellitus reiterated the main features of the human disease: increased blood glucose with development of severe diabetes induced by lack of insulin secretion in response to glucose. As diabetes progresses, these mice show reduction in body weight, among other whole body abnormalities (Remedi et al. 2009 Cell Metabolism, 9, 140-151).


Diabetic Glucotoxicity

diabetic-glucotoxicity_tamoxifen-induction

Islets from normal mouse pancreas contain lots of insulin that is released to maintain blood glucose at normal levels. Mice –and people– that express a genetic mutation in potassium channel suffer Neonatal Diabetes Mellitus. The mouse model reveals complex secondary changes, including unexpected disappearance of insulin and glucagon from the islets. Importantly, these consequences are prevented by maintenance of normal blood glucose by either islet transplantation or chronic antidiabetic sulfonylurea therapy (Remedi et al. 2009 Cell Metabolism, 9, 140-151).


Loss of β-cell Identity: to be or not to be? A Reversible Process

The marked reduction of insulin-containing β-cells in severely diabetic mice (untreated) is not due to increased cell death (TUNEL), but instead to β-cell dedifferentiation to islet progenitor cells (Neurogenin3, Ngn3 positive red nuclei). Strikingly, this process is reversible with the same dedifferentiated cells re-differentiating to mature insulin-containing β-cells following normalization of blood glucose by intensive insulin therapy (treated) (Wang et al. 2014, Cell Metabolism 19:872-882), challenging the paradigm of permanent β-cell damage in long-standing diabetes.


Antidiabetic Sulfonylureas: Transient vs Permanent Neonatal Diabetes?

Antidiabetic sulfonylurea therapy at disease onset can cause remission of Neonatal Diabetes in mice (Remedi at al., 2008 PLoS Medicine 5(10):1473-1485; Remedi et al. 2011, Diabetes 60: 2515-22). Strikingly, remission of Neonatal Diabetes has also been shown in patients treated with sulfonylureas very early (Marshall et al. 2015, Diabetes care 38:e38-e39)


The Hyperactive Mouse

Neurological features in mice expressing mutant channels in the brain. Hyperactivity, impaired motor coordination and balance, decreased muscle strength (unpublished data).

Contact Information

Principal Investigator

Maria S. Remedi, PhD

Assistant Professor of Medicine and Cell Biology & Physiology

Office Location

848 Southwest Tower (Medical campus)

Office Phone (314) 362-6636

Fax (314) 362-7641

Laboratory Location

846 Southwest Tower (Medical campus)

Lab Phone (314) 747-0437

Mailing Address

660 S. Euclid Ave.

Campus Box 8127

St. Louis, MO 63110

Currently seeking graduate students, post-docs and research fellows.

People

Esmeralda Castelblanco Echavarria, PhD

Visiting Researcher

Esmeralda was born in Inirida, Colombia. She earned her bachelor’s degree in Biology from the Pontifical Xavierian University in Colombia. Then, Esmeralda moved to Spain where she got a M.S. in Microbiology at the Autonomous University of Barcelona in 2008. She then completed her PhD at the University of Lleida in Spain in 2014. Her doctoral research focused on identifying protein and miRNA profiles of value for the diagnosis and/or prediction of thyroid cancer prognosis. For the last six years, her investigation focused on characterizing cardiovascular complications as a subclinical atherosclerotic disease by imaging techniques and its characterization and discovering potential new biomarkers of this condition in prediabetes 1 and type 2 diabetes in Barcelona. Dr Castelblanco joined Dr Remedi’s lab in December 2020. She is currently studying secondary consequences of diabetes in pancreatic an extra-pancreatic tissues in mouse models of diabetes.

Remedi Lab

Zihan Yan

Senior Research Technician

Zihan was born and raised in China. She earned her B.S. in Bioengineering from Jilin University, China. Upon graduation, Zihan moved to St. Louis and earned an M.S. in Biomedical Engineering from Saint University in 2012. Zihan has been working with Dr. Maria Remedi since 2013. In the meanwhile, she completed her M.A. in Statistics at Washington University in 2017. Zihan is interested in dietary effects, drug treatment and genetic changes of Neonatal Diabetes. She is also involved in some studies related to Cantu syndrome. When not in lab, Zihan enjoys photography, traveling, gardening, and spending time with her husband and two children.

Remedi Lab

Shaul Yahil

Doctoral Student, DBBS Graduate Research Assisstant

Shaul was born and grew up in Stony Brook, New York. He received his B.S. in Neural Science and B.A. in Psychology from New York University. Shaul then came to Washington University in St. Louis to pursue a PhD in Neuroscience and joined the lab of Dr. Maria Remedi. His doctoral work focuses on the origins of cognitive deficits in mouse models of neonatal diabetes, which he investigates utilizing a combination of animal behavior studies, electrophysiology, and immunohistochemistry. Outside of the lab, he enjoys climbing and outdoor activities.

Remedi Lab

Sumit Patel

Doctoral Student, DBBS Pre Doc Trainee

Sumit was born in Eldoret, a town located in the Great Rift Valley in Kenya. He attended St. Cloud State University in St. Cloud, Minnesota, where he graduated with a B.S. in Biotechnology. He then enrolled in a Master of Science in Biology program at the University of Louisiana at Monroe. He worked on the molecular and physiological mechanisms by which obesity predisposes humans to disease utilizing Drosophila melanogaster as a model. Upon completion of his Master’s in 2020, he moved on to pursue his Ph.D. in Molecular Cell Biology program at Washington University in St. Louis. He joined the lab of Dr. Maria Remedi to understand the underlying mechanisms in the development and progression of type 2 diabetes (T2DM) and to determine the role of autophagy in diabetes. During his free time, he enjoys watching sports (a big fan of Manchester United), reading and being outdoors.

Remedi Lab

Carly Feldman

Undergraduate Research

Carly is an undergraduate student majoring in Psychological Brain & Sciences and on the pre-medical track at Washington University in St. Louis (Class of 2021). She is involved in Life Outside Violence, an organization that assists gun-shot victims in the St. Louis area and is a former member of the Varsity Women’s Tennis team. Outside of the lab, she enjoys running, traveling, and listening to music. Carly joined the Remedi Lab in 2020, she is performing her Bio500 research under the direction of Dr Esmeralda Castelblanco and Dr Maria Remedi.

Remedi Lab

Sophia Chen

Undergraduate Research

Sophia is an undergraduate student majoring in Biology on the Molecular Biology and Biochemistry track and minoring in Psychological and Brain Sciences at Washington University in St. Louis (Class 2023). Sophia is also on a pre-medical track. She is involved in China Care, an organization focused on connecting Chinese adoptees in the St. Louis area with Chinese culture, as well as Firm Foundations, a volunteer-based tutoring center serving the St. Louis community. Outside of the lab, she enjoys cooking, baking, drawing, and taking care of her plants. Sophia joined the Remedi Lab in 2019, she is performing her Bio200 research under the direction of Dr. Amy Clark and Dr. Maria Remedi.

Remedi Lab

Lee Steins

Undergraduate Researcher

Lena is an undergraduate student majoring in Biology on the Molecular Biology and Biochemistry track at Washington University in St. Louis (Class of 2024). Lena is also on a pre-medical track. She is involved with Habitat for Humanity, an organization focused on eliminating poverty and providing housing for individuals in the St. Louis area. Outside of the lab she enjoys hiking, baking, and going to the movies. Lena joined the Remedi Lab in 2021; she is performing research under the direction of Dr Esmeralda Castelblanco and Dr. Maria Remedi.

Remedi Lab

Former Lab Members

Zeenat Asghar Shyr – Postdoctoral Fellow. 2016-2019

Manuela Fortunato – Research Technician. 2017-2018

Christopher Emfinger – PhD student, graduated in 2018

Hannah Conway – Research Technician I, 2016-2019

Alecia Welscher – Research Technician I, 2014-2016

Zhiyu Wang – Clinical Fellow, Washington University

Reka Lorincz – Visiting PhD student, University of Innsbruck – Austria 2017-2018

Stephanie Schiffert   NIH Medical Student Summer Research Program, University of Central Florida. 2019

William McAlister- NIH Medical Student Summer Research Program, Brody School of Medicine. 2018

Erin Lindsey – NIH Medical Student Summer Research Program, Saint Louis University. 2017

Amanda Piaruli – NIH Medical Student Summer Research Program, Drexel University. 2016

Undergraduate students

Gabrielle McGinn – Undergraduate student, Washington University. 2019-2020

Matt Fuess – Undergraduate student, Washington University. 2018-2020

Erin Egan – Undergraduate student, Washington University. 2017-2019

Yixi Wang – Undergraduate Student, Washington University. 2016-2018

Arsam Nadeem – Undergraduate Student St. Louis College of Pharmacy. 2016

Leah Yuan – Undergraduate Student, Washington University. 2015-2017

Betsy Abraham- Undergraduate Student St. Louis College of Pharmacy. 2016

Nihar Shah –Undergraduate student, Washington University. 2015-2016

Jonathan Friedman – Undergraduate student, Washington University. 2012-2014

Summer Students

Bailee Rasmussen – Undergraduate summer student, Utah State University. 2019

Eric Hilker – Undergraduate summer student, Truman University 2016

 Mariana Alisio – Undergraduate summer student – Washington University, 2015

Hannah Conway – Undergraduate summer student, Loyola University, 2015

Nathan York – Undergraduate summer student, University of Missouri, 2011, 2012

Felesha Clake – High School student, St Louis, 2015