Genetics of Mitochondria and Metabolic Syndromes
Yale University Departments of Medicine and Genetics
300 Cedar St., TAC340
New Haven, CT 06520
Ph: 203-464-9420 FAX: 203-785-7560
Ali.Hariri@yale.edu
Hypertension and dyslipidemia are risk factors for atherosclerosis and occur together more often than expected by chance. Although this clustering suggests shared causation, unifying factors remain unknown. We describe a large kindred with a syndrome including hypertension, hypercholesterolemia, and hypomagnesemia. Each phenotype is transmitted on the maternal lineage with a pattern indicative of mitochondrial inheritance. Analysis of the mitochondrial genome of the maternal lineage identified a homoplasmic mutation substituting cytidine for uridine immediately 5’ to the mitochondrial tRNAIle anticodon. Uridine at this position is nearly invariate among tRNAs because of its role in stabilizing the anticodon loop. Given the known loss of mitochondrial function with aging, these findings may have implications for the common clustering of these metabolic disorders.
Biographical Information
Current Position |
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| Fellow, Section of Nephrology, Yale University | |
| 1995 - 1999 | Internal Medicine Residency, Clinical Investigator Pathway, Case Western Reserve University, Cleveland, OH |
| 1999 - | Nephrology Fellowship, Yale University School of Medicine, New Haven, CT |
Education |
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| 1984 - 1989 | CSUF, Fullerton, CA, B.S. (with High Honors, Outstanding Senior), Biochemistry |
| 1989 - 1995 | UCSD School of Medicine, La Jolla, CA, M.D, (Outstanding thesis) |
Research Training |
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| 1990 - 1992 | Chemical Characterization of Activin Receptors, Clayton Foundation, Salk Institute, La Jolla, CA (Mentor: Wylie Vale, PH.D.) |
| 1992 - 1995 | The Interaction of Skn-1 and Tst-1 with Human Papillomaviruses, HHMI, UCSD, La Jolla, CA (Mentor: Michael G. Rosenfeld, M.D.) |
| 1997 - 1999 | The Role of EGFR in Nephrogenesis, Case Western Reserve University, Cleveland, OH (Advisor Terry Magnuson Ph.D. and Ellis Avner M.D.) |
| 2000 - | The Mitochondrial Regulation of Metabolic Disorders, Yale University, New Haven, CT (Mentor: Richard Lifton, M.D./ Ph.D.) |
Teaching Experience |
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| 2002 - | Instructor, Preclinical Clerkship, Yale University |
| 2004 - | Teaching Assistant, “Writing a Successful Grant,” Investigative Medicine, Graduate Program, Yale University |
Committees |
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| 1998 | Organizing Committee on “Entropy, Evolution and Organizing systems” |
| 1989 - 1995 | Committee on Education Policy, UCSD School of Medicine |
| 1990 - 1995 | Committee on Admissions, UCSD School of Medicine |
Journal Reviews |
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| 1991 - 1992 | Western Journal of Medicine Advisory Board for Ob./Gyn |
| 1991 - 1995 | Western Journal of Medicine, Advisory Board for Medicine |
| 1993 - 1995 | Western Journal of Medicine, Advisory Board for Dermatology |
| 2001 - | Critical Care Medicine |
| 2004 - | American Journal of Physiology: Endocrine and Metabolism |
| 2004 - | Nature Genetics |
Honors and awards and lectures |
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| 1989 | American Chemical Society, Outstanding Senior |
| 1989 | Conference of California State University Alumni, Outstanding Senior |
| 1989 | Phi Lambda Upsilon, Honorary Chemistry Society |
| 1989 | Golden key Honor Society |
| 1989 - 1993 | California Graduate Fellowship |
| 1990 | NIH Summer Research Fellowship (Declined) |
| 1990 | Clayton Foundation Fellowship |
| 1993 | UCSD MSTP Fellowship (Declined) |
| 1993 - 1995 | Lucille P. Markey Charitable Foundation, Fellow |
| 1995 | Outstanding Research Thesis, UCSD School of Medicine |
| 2001 | American Society of Nephrology Professional Development Award |
| 2002 | Invited Speaker American Society of Nephrology |
| 2002 - 2004 | National Institute of Health, Loan Repayment Program |
| 2002 - 2004 | American Heart Association, Fellow |
| 2004 - | American Heart Association, Fellow to Faculty Transition Award |
| 2005 | Invited Speaker, University of Iowa, Cardiovascular Research Group |
| 2005 | Invited speaker, University of Southern California, Renal Rounds |
Publications
Original Papers:
- Hariri, A., Weber, B., Olmsted J. III (1990) On the Validity of Shannon- Information calculations for Molecular Biological Sequences. J. theor. Biol. 147, 235-52.
- Andersen, B., Hariri, A., Pittelkow, M., Rosenfeld, M.G( 1997) Characterization of Skn-1a/I POU domain factors and linkage to Papillomavirus gene expression. J. Biological Chemistry 272, 15905-13.
- Wilson, F., Hariri*, A., Farhi, A., Zhao, H., Petersen, K., Nelson-Williams, C., Raja, K., Kashgarian, M., Shulman, G., Scheinman, S., Lifton, R (2004). A Cluster of Metabolic Defects Caused by Mutation in a Mitochondrial tRNA. Science 306, 1190-4 .
- Hariri, A., Sweeney, W., Avner, E, The Epidermal Growth Factor Receptor Regulation of Nephrogenesis is Strain Dependent. Submitted Pediatric Nephrology.
Abstracts:
- Mathews, L. Hariri, A., Vale, W., (1991). Characterization of Activin A Receptors by Chemical Cross linking. Endocrine Society.
- Hariri, A., Andersen, B., Rosenfeld, M.G., (1993). POU Domain Factors in Skin. Gordon Research Conference on Epithelial Differentiation and Keratinization.
- Hariri, A., Sweeney, W., Magnuson, T., Avner, E. (1999). Renal Development and Function in Epidermal Growth Factor Receptor (EGFR) Null Mice. American Society of Nephrology.
- Sanjad, S., Hariri, A., Habbal, Z., Lifton, R (2002). Novel Mutations in the Paracellin-1 gene (PCLN-1) in Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis and atypical phenotype. Pediatric Academic Societies
- Hariri, A., Wilson, F., Scheinman, S., Lifton, R (2004). Hypertension, hypercholesterolemia, and hypomagnesemia due to mitochondrial mutation. Council for High Blood Pressure Research.
Book:
- Hariri, A.. Renal defects due to mitochondrial mutations. In Genetic Diseases of the Kidney, edited by R.P. Lifton, S. Somlo, G.H. Giebisch, and D.W. Seldin. Elsevier, 2005, in press.
