| Biography: Dr. Nazli McDonnell graduated from University College Cork and Towson University with a B.A. degree in philosophy and a B.S. degree in chemistry and biology. She subsequently worked as a research assistant in Dr. Jeff Corden's laboratory at Johns Hopkins Medical School, Department of Molecular Biology and Genetics. She completed the M.D./Ph.D. program in University of Maryland Medical School in 1998. Her Ph.D. supervisor was Dr. Michael Summers in the Department of Biochemistry and Molecular Biology at the University of Maryland, Baltimore County. The focus of Dr. McDonnell's Ph.D. research was the study of protein-drug interactions by Nuclear Magnetic Resonance Spectroscopy. Dr. McDonnell's clinical training consisted of a residency in Internal Medicine at York Hospital, Pennsylvania, and a Medical Genetics Fellowship at the Metropolitan Washington D.C. Genetics Fellowship Training Program at National Human Genome Research Institute at the National Institutes of Health. In 2003, Dr. McDonnell joined Dr. Clair Francomano's laboratory at the National Institute on Aging, Laboratory of Genetics to study hereditary disorders of connective tissue. Upon Dr. Francomano's departure, she moved to the Laboratory of Clinical Investigation. Her professional memberships include Sigma Xi, American Medical Association, American Women's Medical Association, American Association for the Advancement of Science, American Society of Human Genetics, and Phi Kappa Phi. |
| Research Interests: Dr. McDonnell's research is focused on clinical and molecular investigations of hereditary disorders of connective tissue (HDCT). The disorders of interest are Ehlers-Danlos syndrome (EDS), Marfan syndrome, Stickler syndrome, hereditary aneurysm syndromes and fibromuscular dysplasia (FMD). Dr. McDonnell is investigating the natural history of these disorders at the NIA-ASTRA Unit, as well as studying genotype/phenotype correlations, molecular and cellular mechanisms and exploring treatment strategies in the laboratory. |
| Current Clinical Projects - Natural History of Hereditary Disorders of Connective Tissue: We are investigating the cardiovascular and musculoskeletal complications of hereditary disorders of connective tissue, including autonomic dysfunction observed in patients with EDS, incidence of aneurysms and cardiovascular abnormalities in patients with all forms of HDCT, incidence of spine abnormalities and bone density loss in patients with HDCT, and pain and quality of life issues associated with HDCT. These investigations, in collaboration with Drs. Bolognese and Milhorat, has uncovered a predisposition to craniocervical junction abnormalities including Chiari I malformation in patients with HDCT. We are also enrolling a group of patients with a diagnosis of FMD in order to define this disorder clinically and discover causative genes. |
| Current Laboratory Projects: In collaboration with Dr. Mark Talan's group, we are working with a mouse model of VEDS to discover and assess treatment strategies for VEDS. Other investigations include the role of tenascin X (TNXB) mutations and deletions in Hypermobile EDS and in patients with Congenital Adrenal Hyperplasia (in collaboration with Dr. Debbie Merke), the study of genotype/phenotype correlations in Stickler Syndrome (with Dr. Ala-Kokko), discovery of new causative genes for familial aneurysm syndromes and in families with HDCT where no mutation in the known genes such as COL5A1, COL5A2, COL2A1, COL11A1, COL3A1, TGFBR1, TGFBR2 or fibrillin has been identified (with Dr. Andrew Singleton). Other projects on the horizon include siRNA treatment strategies for dominantly inherited genetic disorders. |
| Principal Investigator, IRB approved protocol, National Institute on Aging: Project # 2003-86: "Clinical and Molecular Manifestations of Heritable Disorders of Connective Tissue." Patients with hereditary disorders of connective tissue have many early manifestations that usually afflict the elderly including osteoarthritis, loss of bone density, spinal disc disease, musculoskeletal weakness, arterial aneurysms, and alterations in vascular remodeling. Through clinical and laboratory evaluations in this group of patients, we expect to elucidate underlying mechanisms contributing to these common conditions associated with aging. |
| Recent Publications: |
- McDonnell NB, Gorman BL, Mandel KW, Schurman SH, Assanah-Carroll A, Mayer SA, Najjar SS, Francomano CA. Echocardiographic findings in classical and hypermobile Ehlers-Danlos syndromes. Am J Med Genet A. 2006;140(2):129-136. [Abs]
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