Genome Technology Center

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

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

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


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

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

2002 - Instructor, Preclinical Clerkship, Yale University
2004 - Teaching Assistant, “Writing a Successful Grant,” Investigative Medicine, Graduate Program, Yale University


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

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

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


Original Papers:

  1. 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.
  2. 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.
  3. 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 .
  4. Hariri, A., Sweeney, W., Avner, E, The Epidermal Growth Factor Receptor Regulation of Nephrogenesis is Strain Dependent. Submitted Pediatric Nephrology.


  1. Mathews, L. Hariri, A., Vale, W., (1991). Characterization of Activin A Receptors by Chemical Cross linking. Endocrine Society.
  2. Hariri, A., Andersen, B., Rosenfeld, M.G., (1993). POU Domain Factors in Skin. Gordon Research Conference on Epithelial Differentiation and Keratinization.
  3. 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.
  4. 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
  5. Hariri, A., Wilson, F., Scheinman, S., Lifton, R (2004). Hypertension, hypercholesterolemia, and hypomagnesemia due to mitochondrial mutation. Council for High Blood Pressure Research.


  1. 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.

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