University of Iowa Carver College of Medicine leaders have launched a new initiative this fall to call attention to impactful and innovative research articles by the college’s faculty and staff.
The “Best Research Paper Awards” were given to Carver College of Medicine faculty who served as authors on articles published in peer-reviewed journals over the past year. Awards were presented in three categories: basic, clinical, and educational research.
Congratulations to Drs. Potthoff and Crawford on Receiving a Collaborative Pilot and Feasibility Grant Award
Liver-brain crosstalk is now recognized as a fundamental driver of feeding behavior and body weight regulation, which are primary determinants of obesity and type 2 diabetes. Both nutrient fuels and hormones serve as signals from the liver to the brain. A key metabolic fuel that is produced in the liver but serves important roles in the brain is the ketone body. Ketones are produced in the liver, and are by-products of burned fat, serving as an important fuel source for the brain’s neurons. Through unclear mechanisms, ketones also modulate feeding behavior and body weight through actions upon a fundamental energy and metabolism coordinating center in the brain called the hypothalamus. In addition to ketones, the liver also produces the hormone fibroblast growth factor 21 (FGF21) which signals to hypothalamic neurons. However, nothing is known about how hypothalamic function is coordinately regulated by ketones and FGF21 together. This Pilot and Feasibility application proposes the key initial experiments that will address this critical knowledge gap. The proposed experiments forge a new collaboration between an expert in integrated ketone metabolism, metabolomics, and metabolic flux analysis (Crawford) and a co-PI who is an FGF21 signaling expert who is uniquely skilled in targeting, manipulation, and quantifications of hypothalamic neuronal signaling in vivo and ex vivo (Potthoff). The approaches described here will be the first to determine how ketones modulate hypothalamic signaling in response to FGF21, and whether their cooperative effects are dependent on ketone oxidation in neurons.
Potthoff, one of six named UI Health Care Distinguished Scholars Program
Dr. Potthoff studies energy homeostasis and metabolism, particularly in the liver. In particular, Dr. Potthoff focuses on the many roles of the liver hormone FGF21 in controlling multiple functions in a variety of tissues such as the central nervous system that may contribute to obesity and other metabolic diseases.
An initiative meant to catalyze new discovery, the DSP will name six new scholars next year and the year after, supporting a total of 18 scholars at a time. Scholars named to the program will have the option of submitting renewal applications at the end of their term. The other five scholars named with Potthoff are Christopher Ahern, PhD, professor of Molecular Physiology and Biophysics; Maria Spies, PhD, professor of Biochemistry; David Stoltz, MD, PhD, professor in Pulmonary, Critical Care and Occupational Medicine; Samuel Young, PhD, associate professor of Anatomy and Cell Biology; and Jian Zhang, MD, professor of Pathology.
Sharon Idiga presentation at the Molecular Medicine Research Retreat earns 1st place award
Sharon Idiga, graduate student in Dr. Matthew Potthoff's laboratory, was awarded 1st place on her oral presentation entitled "Low Protein Diet Improves Metabolic Health through a Novel Endocrine Circuit" at the Molecular Medicine Research Retreat.
Sheps King-McAlpin receives NIH R01 Minority Supplement
Sheps King-McAlpin, a graduate student in Dr. Matthew Potthoff’s laboratory in the Molecular Medicine Program and Department of Pharmacology, has been awarded an NIH R01 Minority Supplement for his project entitled, “Exploring the Mechanism of FGF21’s Acute Insulin Sensitization.” The main objective of his project is to determine how the endocrine hormone FGF21 acts in brown adipose tissue to increase insulin sensitivity. Sheps’ studies will utilize unique genetic models and proteomic techniques to elucidate the signaling pathway activated by FGF21 to increase insulin-dependent glucose uptake.
Lucas BonDurant completes his PhD
Lucas D. BonDurant has completed his graduate work in the laboratory of Dr. Matthew Potthoff and will graduate with his PhD in May 2018. His thesis title was "The Regulation of Glucose Homeostasis by FGF21." BonDurant's dissertation work focused on the mechanism of FGF21 in regulating glucose homeostasis through enhancing insulin sensitivity, increasing energy expenditure, and decrease simple sugar intake in an effort to define FGF21's pharmacological and physiological effects. Members of his thesis committee were chair, Dr. Matthew Potthoff, Drs. Justin Grobe and Kamal Rahmouni from the Department of Pharmacology, Dr. Ling Yang from the Department of Anatomy and Cell Biology, and Dr. Eric Taylor from the Department of Biochemistry.
Lucas received his BS in Cell and Molecular Biology from Missouri State University and entered the Molecular and Cell Biology Program (now Molecular Medicine Program) at the University of Iowa in 2014. Throughout his graduate training, Lucas was selected to present his research at multiple venues including a Keystone Conference in Colorado and an EMBO Workshop in Portugal. He will be starting a Research Scientist position at Alnylam Pharmaceuticals in April 2018.
Magdalene K. Ameka completed her graduate work in the laboratory of Dr. Matthew Potthoff graduating with her PhD in August 2017. Her thesis title was "The Role of Fibroblast Growth Factor 21 (FGF21) in Regulating Energy Homeostasis." Magdalene's dissertation work focused on the mechanism of FGF21 in regulating energy expenditure, body weight and glycemia in an effort to define how FGF21 has anti-obesogenic and anti-diabetic effects. Members of her thesis committee were chair, Dr. Matthew Potthoff from the department of Pharmacology, Drs. Curt Sigmund, Justin Grobe, and Anne Kwitek from the department of Pharmacology, and Frederick Domann from the department of Free Radical Biology.
Dr. Ameka received her BS in Biochemistry and Biophysical Sciences from the University of Houston and entered the Molecular and Cell Biology Program (now Molecular Medicine Program) at the University of Iowa in 2013. She officially joined the Potthoff lab in the Department of Pharmacology in 2014 to begin the Ph.D. phase of her training. Dr. Ameka will be conducting a postdoctoral fellowship in the laboratory of Dr. Alyssa Hasty at Vanderbilt University starting September 2017, where she will be investigating the role of iron handling in macrophages during obesity.
CONGRATULATIONS to Dr. Ameka!
Lucas BonDurant, a graduate student in Dr. Matthew Potthoff’s laboratory, presented his research at the joint Keystone Diabetes and Adipose Tissue and Obesity Conference in Keystone Colorado. He was selected to give an oral presentation, entitled “FGF21 Acutely Enhances Insulin Sensitivity." Lucas is currently a 3rd year graduate student in the Molecular and Cellular Biology Program, is a Sloan Scholar, and is supported by the Pharmacology T32 Training Grant.
Kathleen Markan who is completing a post-doctoral fellowship in the laboratory of FOEDRC member Dr. Matthew Potthoff was recently awarded a K01 Research Scientist Development Award from the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK). She will receive $526,191 over 4 years of the award. Dr. Markan will be joining the faculty of the Department of Pharmacology.
The Proposal is entitled: “A Novel Mechanism to Increase the Beiging of White Adipose Tissue”
Obesity is characterized by excessive accumulation of fat tissue which occurs when energy storage exceeds energy expenditure. In turn, this can result in the deposition of lipid in non-adipose organs precipitating many of the adverse health outcomes associated with the condition. Therefore, methods of increasing energy expenditure in fat tissue could offer new therapeutic avenues for the treatment of obesity. Beige adipocytes are specialized fat cells found within white fat depots that become activated in response to various stimuli such as cold exposure. Activated beige adipocytes express a protein known as uncoupling protein-1 (UCP-1) which essentially allows excess energy, such as glucose and lipid, to be dissipated as heat. Accordingly, beige adipocytes could be harnessed as a means to essentially burn off excess energy and prevent excessive fat accumulation. However, little is known regarding the development of these specialized fat cells. In this regard, the transcription factor TBX1 has been identified in beige adipocytes; yet, nothing is known regarding its metabolic or transcriptional role. To begin to address this, we have generated novel in vivo models in which we have deleted or overexpressed TBX1 in a fat cell specific manner. Our studies will unite advanced physiological techniques and large scale molecular and bioinformatic analysis in order to determine the role of TBX1 in the development and metabolism of beige adipocytes. Collectively, our studies will provide immediate and long-term information regarding the role of TBX1 in beige adipocytes which in turn may provide clinically relevant insight regarding the development and potential treatment of obesity.
Magdalene Ameka, a graduate student in Dr. Matt Potthoff’s laboratory, won the People’s Choice Award at the 3 Minute Thesis Competition of the UI Graduate College. One of sixteen finalists, she competed in the final round in November in the Art Building West, presenting a talk that described her thesis research entitled “Lose the Weight by Ignoring the Fat.”
Magdalene is a third year Molecular and Cellular Biology Program graduate student doing her thesis research in Pharmacology. She came to the US from Kenya in 2006, and received a Bachelor’s degree in 2009 from the University of Houston in Biochemistry and Biophysical Sciences. She is currently working to understand how the liver-derived hormone fibroblast growth factor 21 (FGF21) regulates energy homeostasis. In whatever free time grad school allows her, she likes to be outdoors enjoying good food, good wine and good music.
The 3 Minute Thesis Competition challenges graduate students to communicate their research in three minutes or less in non-specialist language. Learn more about all the finalists on the finalist spotlight website.
Lucas BonDurant, a graduate student in the laboratory of Matthew Potthoff, PhD, was selected to give an oral presentation at the EMBO Conference “Neural control of metabolism and eating behavior conference” in Cascais, Portugal.
Omar Shaban, an undergraduate researcher in the laboratory of Matthew Potthoff, PhD, has been accepted into the Iowa Biosciences Academy (IBA). IBA is funded by the National Institutes of Health (NIH) through an Initiative for Maximizing Student Development (IMSD) grant and its mission is to promote a diverse and inclusive community of undergraduate researchers with aspirations for a PhD in the biosciences. Omar’s research project will be to examine mechanisms regulating fuel utilization in adipose tissue.
Sarah Small, an undergraduate researcher in the laboratory of Matthew Potthoff, PhD, has been selected to receive an Undergraduate Summer Research Fellowship from the American Heart Association (AHA). Sarah’s research project will be to examine a novel mechanism to reverse insulin resistance.
Ms. Magdalene Ameka, a graduate student in Dr. Matthew Potthoff’s lab in the Department of Pharmacology, received a Graduate College Post-Comprehensive Research Award based on her strong academic record. Magdalene will receive a generous stipend from the Graduate College during the spring 2016 semester.
Dr. Matthew Potthoff, PhD, an Assistant Professor in the Department of Pharmacology, has been awarded a National Institute of Health (NIH) R01 Research Grant for his project, titled “Regulation of Carbohydrate Metabolism by FGF21 Action on Brown Adipose Tissue." The goal of this research is to determine the mechanism for the glucose lowering effects of the endocrine hormone fibroblast growth factor 21 (FGF21). FGF21 is currently being pursued as a potential therapeutic for the treatment of obesity and diabetes.
Kathleen R. Markan, PhD, a postdoctoral scholar in the laboratory of Matthew Potthoff, assistant professor of pharmacology has been awarded an NIH Postdoctoral Ruth L. Kirschstein National Research Service Award for her project titled, “A Novel Therapeutic Approach to Combat Nonalcoholic Fatty Liver Disease." The main objective of her project is to determine the role of Tox, a novel transcription factor, in the development of metabolic dysfunction. Dr. Markan’s studies will utilize unique genetic models and advanced radio-isotope tracer techniques to delineate the in vivo effects of Tox upon liver metabolism.
Circulating FGF21 is Liver Derived and Enhances Glucose Uptake During Refeeding and Overfeeding published in Diabetes
Matthew Potthoff, PhD, assistant professor of pharmacology recently published an article in Diabetes titled, “Circulating FGF21 is Liver Derived and Enhances Glucose Uptake During Refeeding and Overfeeding.” Dr. Potthoff’s laboratory discovered that fibroblast growth factor 21 (FGF21), an endocrine hormone that is expressed in multiple tissues and functions physiologically to maintain energy homeostasis, functions physiologically as an insulin sensitizer under conditions of acute refeeding and overfeeding. Their study shows that liver-derived FGF21 enters the circulation during fasting, but also remains present and functional during the early stage of refeeding. FGF21 is being pursued as a therapeutic target for diabetes and obesity because of its rapid and potent effects on improving insulin sensitivity.
Drs. Matthew Potthoff, PhD and Eric Taylor, PhD, Assistant Professors in the Department of Pharmacology and Biochemistry, respectively, have been awarded a Carver Collaborative Grant. The project, titled “Regulation of Hepatic Gluconeogenesis by the Mitochondrial Pyruvate Carrier,” is focused on understanding the role of mitochondrial pyruvate carrier (MPC) proteins in regulating hepatic metabolism. This project aims to determine whether decreasing MPC activity can reduce the excessive hepatic glucose production associated with type II diabetes.
Dr. Matthew Potthoff, PhD, an Assistant Professor in the Department of Pharmacology, has been awarded an Edward Mallinckrodt, Jr. Foundation Grant. The project titled “A Novel Therapeutic Approach to Combat Obesity and Metabolic Syndrome, is focused on understanding the mechanisms contributing to hormone resistance during diet induced obesity and identifying potential targets to reverse these effects.
Dr. Matthew Potthoff, PhD, an Assistant Professor in the Department of Pharmacology, has been awarded an American Diabetes Association Junior Faculty Award for his project, titled “Targeting the transcription factor Tox as a therapeutic for nonalcoholic fatty liver.” The goal of this research is to determine the role of Tox is regulating carbohydrate and lipid metabolism and to explore its role in the development of NAFLD.
Dr. Matthew Potthoff, PhD, an Assistant Professor in the Department of Pharmacology, has been awarded a Carver Medical Research Initiative Grant. The project, titled “Targeting FGF21 Production as a Therapeutic for Obesity and Metabolic Syndrome,” is focused on understanding the mechanisms regulating FGF21 production. The goal of this research is to identify mechanisms to increase endogenous FGF21 expression as a treatment for metabolic disease.