Department of Medicine

Endocrinology, Diabetes & Metabolism Faculty

Nicholas E. Simpson, Ph.D.,
Research Assistant Professor of Medicine

Professional Summary

Dr. Simpson received his Ph.D. in Cancer Biology from Wayne State University, Detroit MI, in 1997. As a graduate student, mentored by Dr. Jeffrey Evelhoch, he was a recipient of an institutional NRSA Training grant and a grant from the American Cancer Society. He trained as a post-doctoral fellow under the direction of Dr. Ioannis Constantinidis at Emory University, Atlanta GA, and was the recipient of an individual NRSA Fellowship. Dr. Simpson joined the University of Florida Faculty of the Department of Medicine in the Division of Endocrinology in January 2002. A list of his publications can be accessed by clicking here.

Laboratory Research Summary

Prior to graduate school, Dr. Simpson was involved in a number of studies using NMR to study physiological effects of novel cancer therapeutics. His doctoral dissertation research involved developing and optimizing apparatus and NMR methods which allow for non-invasive absolute measurements of tissue perfusion. Dr. Simpson’s post-doctoral work studied the link between the cellular bioenergetics and the secretion of insulin in transformed cell lines using ¹³C and ³¹P NMR spectroscopic techniques. He was also involved in amino acid analog research aimed at obtaining tumor-specific PET-visible diagnostic agents.

Presently, Dr. Simpson directs research in the Endocrinology Division's "Laboratory for Tissue Engineering", and he is a Principal or co-investigator on a number of currently funded grants, which are briefly outlined below. A major research focus of the "Laboratory for Tissue Engineering" is concerned with studying a tissue construct comprised of insulin-secreting cells entrapped in a matrix (an aptly named ‘bioartificial pancreas’). These substitutes may someday be used as a replacement for the insulin-secreting cells that have failed in persons with Diabetes (particularly Type 1). Through bioanalytical, histological and NMR techniques, the relationship between cellular growth/function and the composition of the construct is being determined. Additionally, the coupling between energy metabolism and insulin secretion in insulin-secreting cell lines can be quantitatively assessed through NMR spectroscopic techniques. Though much is known about the mechanism of insulin secretion, the significance and contribution of the bioenergetic status to secretion remains unresolved. By determining critical metabolic pathways, new targets for engineering metabolically superior surrogate cell lines can be distinguished. These NMR approaches have major implications for the research of any cell system where energetics plays a role in the function of the cell.

Another research interest involves studying antioxidants (which play a role in combating oxidative stress found in aging processes, cancer, neurodegenerative diseases and diabetes) through novel NMR-based methods to track antioxidant metabolism in the brain and in cancer. Additionally, there are ongoing pilot studies looking at mitochondrial processes in diabetes, cancer, and rare inborn errors of metabolism using NMR spectroscopic techniques and computer modeling analysis.

Principal Investigator: NIH R01 DK047858
“A study of model ß-cells in diabetes treatment”

The overarching goal of this project is to develop a noninvasive method to monitor the in vivo function of an implanted insulin-secreting construct (containing entrapped insulin-secreting cells surrounded by a tuned coil) through NMR spectroscopy and imaging. The hypothesis is that NMR-detectable indices can monitor the function of an implanted construct and predict its failure prior to loss of euglycemia.

There are three major specific aims associated with this study:

1) optimize the in vivo NMR signal from the construct through designing and optimizing inductively-coupled RF coils to be used with the implant.
2) create time-dependent O₂ and cell density gradients in the constructs and validate the non-invasive NMR-visible measurements with invasive standard methods.
3) non-invasively assess the function of the implanted construct (in mice) through NMR methods and correlate changes in NMR indices to changes in physiologic events so that construct function can be measured and its failure predicted.

Principal Investigator (subcontract): NIH R01 DK073991
“Cryopreservation of tissue engineered substitutes”

This subcontract is to perform NMR experiments that address metabolic and functional questions regarding cryopreserved insulin-secreting constructs. There are two major roles: (1) use NMR microscopy (microimaging) to assess the effects of cryopreservation on the integrity of the extracellular matrix and surrounding PLL layer of the constructs; (2) perform in vitro ¹³C/³¹P NMR spectroscopic studies on extracts of cryopreserved constructs to determine the metabolic effects of cryopreservation.

Principal Investigator (subcontract): NIH R01 DK076801
“Tissue engineered substitute based on a system of autologous cells”

This subcontract focuses on NMR methods that can address metabolic and functional questions regarding the tissue engineered pancreatic substitute. There are two thrusts to this work: (1) perform in vitro ¹³C/³¹P NMR spectroscopy on hepatic and enteroendocrine cells that have been genetically modified to secrete insulin and determine the relationship between cellular energetics and the insulin-secreting ability of the cells; (2) perform in vivo ¹H NMR spectroscopy/imaging of implanted tissue substitutes (in mice) to measure NMR indices and estimate construct function.

Co-investigator: NIH R01 CA114365
“Noninvasive monitoring of glutathione metabolism in tumors”

This project aims to develop magnetic resonance imaging techniques to measure in vivo tumor glutathione levels following administration of an NMR-visible tracer. The technique holds promise as an early indicator of the success of therapy, and as such, brings advancement to the field of clinical oncology.

Co-investigator: NIH R21 AG029994
“Spectroscopic imaging of antioxidant metabolism in the brain”

This project centers on developing noninvasive magnetic resonance spectroscopic imaging techniques to follow the uptake, distribution and metabolism of antioxidants and glutathione in the rat brain. It is a study of the antioxidant metabolic pathways that protect the brain against oxidative damage, which unchecked, lead to neurodegeneration.

Principal Investigator: National High Field Magnet Laboratory Pilot Project
“¹³C isotopomeric studies of islet metabolism using a high-field cryogenic microcoil NMR system”

This project will permit us to characterize key metabolic pathways associated with insulin secretion in the native islet using NMR micro-cryoprobes. It will also provide critical information regarding the role of aspartate in both the native islet and a surrogate cell line.

Co-investigator: National High Field Magnet Laboratory Pilot Project
“Carbon flux in hypoxic cancer cells”

This project examines the contribution of the PPP to the metabolic phenotype of cancer cells. It uses ¹³C-isotopomer analysis to examine carbon flux through glycolysis and PPP and correlate differences in flux to the known metastatic potential of breast cancer cells. A hypothesis is that results from these studies will lead to new targets for therapeutic intervention.