In vivo Modeling Implicates APOL1 in Nephropathy: Evidence for Dominant Negative Effects and Epistasis under Anemic Stress.

A major focus of both my clinical practice and investigative work is the diagnosis and treatment of disorders affecting solid-organ transplant recipients, particularly infectious complications. For the past 15 years, I have served as the primary pathologist for one of the largest lung transplant programs in the world; in the process contributing to over 20 peer-reviewed publications on complications of lung transplantation, including infections, gastroesophageal reflux, tumors, and antibody-mediated rejection; and writing a major book chapter on the subject (Howell DN and Palmer SM, Pathology of the Lung Transplant. 2006. In: Lynch JP, Ross D, eds. Lung and Heart-Lung Transplantation. Marcel Dekker, Inc., New York, pp. 683-722). I have also been the primary pathologist for Duke's renal and liver transplant programs, authoring or co-authoring a wide variety of journal articles and a book chapter in these areas (e.g., Plumb et al., Transplantation 2006;82:1224-1224; Snyder et al., Am. J. Respir. Crit. Care Med. 2010;181:1391-1396).

A second major area of interest is the pathogenesis of renal glomerular diseases. In collaboration with members of the Division of Nephrology at Duke, I have helped assemble and characterize a large registry of patients with familial focal segmental glomerulosclerosis (FFSGS)(Conlon et al., Kidney Int. 1999;56:1863-1871). Analysis of one of the families in this registry led to the discovery at Duke, in the laboratory of Dr. Michelle Winn, of mutations in the TRPC6 cation channel as a cause of FFSGS (Winn et al., Genomics 1999;58:113-120; Winn et al., Science 2005;308:1801-1804). We are continuing to collect data on additional families with focal segmental glomerulosclerosis. In addition, I have served as principle consultative pathologist for several investigators working in animal models of renal disease and transplantation (e.g., Crowley et al., Hypertension 2010;55:99-108).

Finally, I have devoted considerable time and energy to applications of correlative microscopy to diagnostic pathology, with particular emphasis electron microscopy. I am currently President of the Society for Ultrastructural Pathology, an international organization that promotes the use of ultrastructural examination in both diagnostic pathology and clinical and basic research. Much of my published work in this area involves the role of electron microscopy in the diagnosis of renal diseases (e.g., Howell et al., Ultrastruct. Pathol. 2003;17:295-312; Pavlisko and Howell, Ultrastruct. Pathol., in press), but I have also written extensively, with my colleague Dr. Sara Miller, on the ultrastructural diagnosis of infectious disorders, contributing, among other things, to the first description of a new polyomavirus-induced skin disorder, trichodysplasia spinulosa (Haycox et al., J. Investig. Dermatol. Symp. Proc. 1999;4:268-271).

Dr. Telen is recognized as an expert in the biochemistry and molecular genetics of blood group antigens and the pathophysiological mechanisms of vaso-occlusion in sickle cell disease. She is the Director of the Duke Comprehensive Sickle Cell Center.

Dr. Telen's laboratory focuses on structure/function analysis of membrane proteins expressed by erythroid cells, as well as the role of these proteins in non-erythroid cells. Proteins are also studied in transfectant systems, and research focuses especially on adhesion receptors. The goals of this work are (1) to understand the mechanism and role of red cell adhesion to leukocytes and endothelium in sickle cell disease; (2) to understand the signaling mechanisms leading to activation (and inactivation) of red cell adhesion molecules; (3) to understand the molecular basis of blood group antigen expression, and (4) to understand the interactions of erythroid membrane proteins with other cells and with extracellular matrix..

Recent investigations have focused on the role of signaling pathways in the upregulation of sickle red cell adhesion. Present studies include (1) investigation of beta-adrenergic signaling pathway responsible for activation of B-CAM/LU and LW adhesion receptors; (2) understanding how nitric oxide and ATP downregulate sickle red cell adhesion; (3) studying the effect of these processes in animal models.

Dr. Telen is also involved in a large multicenter study looking for genetic polymorphisms that affect clinical outcomes in sickle cell disease, as well as a multi-center study investigating the mechanisms and treatment of pulmonary hypertension in sickle cell disease.


Key Words:

Adhesion molecules
Erythrocyte membrane
Sickle cell disease
Transfusion medicine
Immunohematology
CD44
B-CAM/LU
Genetic polymorphisms

One of my major research foci is in the genetic basis of psychiatric and neurological disorders. I am currently involved in studies to dissect the genetic etiology of attention deficit hyperactivity disorder (ADHD), autism, chiari type I malformations, essential tremor, and neural tube defects. Additional research foci include genetic modifiers of sickle cell disease, and genetic contributions to birth outcomes, particularly among African American women.