Department of Medicine

Faculty

Mark S. Segal, M.D., Ph.D.

Dr. Segal received a B.S. degree in Biology from MIT in 1984.  As an undergraduate he did research in the laboratory of Dr. Monty Krieger studying the alteration in the glycosylation pattern of a cell line defective in LDL receptor endocytosis.  After graduating from MIT, Dr. Segal was accepted into the MSTP training program at the University of Texas Southwestern Medical School.  He did his Ph.D. dissertation work in the laboratories of Dr. Mary-Jane Gething and Dr. Joseph Sambrook.  He studied the folding pattern of the influenza hemagglutinin protein and its interaction with the heat shock protein BiP. 

After graduating from the M.D./Ph.D. program in 1992, he completed both his internship and residency in Internal Medicine at Parkland Memorial Hospital at Dallas..  In 1995, he started his nephrology fellowship at Beth Israel Hospital under the direction of Dr. Vikas Sukhatme.  During his fellowship,  he worked on a developing a gene therapy vector consisting of a newly created lentiviral vector combined with an adenoviral vector to yield a novel method for gene transduction into the kidney.  For this work he was awarded an NIH Clinical Investigator Award.  In addition, Dr. Segal worked on investigating the mechanism by which endostatin, an anti-angiogenic compound, is completely selective for endothelial cells in tumor vascular beds.  After one year as an Instructor at Harvard Medical School, he joined the Department of Medicine at the University of Florida as an Assistant Professor.

Publications

Research Interest

Endothelial cell apoptosis, ordered cell death, is emerging as an important aspect in the progression of atherosclerosis. However in the context of renal disease, endothelial cell apoptosis has not been well studied despite growing evidence that it may play a role in development of renal insufficiency. Serum from patients with distinct types of acute renal failure, such as the syndrome of hemolytic uremia syndrome and “Scleroderma crises,” has been shown to cause endothelial cell apoptosis. In addition to causing acute injury, apoptosis may also play a role in the progression of renal disease. In the five-sixths nephrectomy rat model, where the loss of nephron mass leads to further decline in renal function, apoptosis of glomerular endothelial has been shown to occur. Could the tendency of an individual’s endothelial cell to undergo apoptosis be a critical factor in whether that individual will develop renal disease? Experimentally, different endothelial cells tolerate varying levels of cellular damage or growth factor withdrawal before undergoing apoptosis. Clinically only a fraction of patients with hypertension will progress to end-stage renal disease and require renal replacement therapy. We are developing methods to test the hypothesis that the susceptibility of endothelial cells to apoptose and the ability of an individual to repair the endothelium underlies the propensity to develop progressive renal disease.

With regard to repair, we are looking at the role that progenitor endothelial cells, derived from the bone marrow, play in the development of intimal hyperplasia and endothelial repair. We have developed a mouse model for venous intimal hyperplasia and are using that to look at the role progenitor cells play in the development of venous intimal hyperplasia. In addition, in patients we are studying the numbers and migratory characteristics of these progenitor cells. We are analyzing the changes that occur with the development of chronic diseases like diabetes, hypertension, and chronic renal insufficiency.

With regard to assessing renal damage, we are studying circulating endothelial cells. These cells are fully mature endothelial cells that circulate in the blood and are increased in a number of conditions that increase endothelial injury. We have found that patients with diabetes and hypertension have increased numbers of these cells. In addition, in patients with end-stage renal disease an increased number of these cells are associated with an increased risk of morbidity and mortality. We are studying whether the number of these cells can be altered by better blood pressure control or better diabetic control.

Third, we are developing assays to quantitatively determine the tendency of endothelial cells to undergo apoptosis. With these assays we plan to study the effect of the cytosolic milieu, potassium and pH, on the tendency of cells to apoptose.

Last, we are investigating the hypothesis that the endothelial cells from patients with malignant hypertension and scleroderma renal crisis have a greater tendency to apoptose. We are growing endothelial cells isolated from patients with specific diagnoses in order to study their apoptotic tendency.