For Scientists Research Information Alumni Connection

Alessandro Doria, M.D., Ph.D.

Dr. Doria is an Investigator in the Section on Genetics and Epidemiology and the Director of the Genetics Core at Joslin Diabetes Center, as well as an Assistant Professor of Medicine at Harvard Medical School. He received his medical degree and doctorate in Endocrinology and Metabolism from the University of Padua in Italy, and completed a fellowship at Joslin Diabetes Center. Before his return to Joslin as an Investigator, he was a Senior Lecturer/Honorary Consultant in Endocrinology and Diabetes at Guy's Hospital and the University of London in Great Britain.

Efforts to map the genes causing type 2 diabetes have been hampered by the heterogeneity of this disorder. Several genes are likely to be involved, interacting with other genes and influenced by environmental factors such as diet and  physical activity. To overcome these challenges, Dr. Doria and his colleagues are studying the genes of individuals with diabetes and their family members.

Through family genome analysis, Dr. Doria and his colleagues found that variants of a gene in adipose (fat) tissue are associated with insulin resistance--a predisposing condition for type 2 diabetes. They also identified several regions of the genome that are likely to host genes that cause diabetes, and are analyzing these regions in detail.

The major cause of death for people with diabetes is  cardiovascular disease, particularly atherosclerosis and coronary artery disease (CAD). Thus, in their search for diabetes genes, Dr. Doria and his colleagues also are trying to identify genes that increase the predisposition to atherosclerosis and CAD. For this study, they are recruiting a large number of patients with type 2 diabetes who have CAD, and an equal number who have not developed CAD despite having type 2 diabetes. Dr. Doria is comparing the DNA of these two groups with the goal of finding gene sequence variations that predispose certain individuals to cardiovascular disease.

Knowledge of these genetic markers may lead to early identification of people at high risk of CAD and to primary preventive programs. Furthermore, functional studies of the genes may lead to a better understanding of the mechanisms of atherogenesis (the formation of abnormal fatty deposits in arteries). This knowledge might suggest new pharmacological or lifestyle interventions to prevent atherosclerosis in people with type 2 diabetes as well as in the general population.

Dr. Doria is working with other investigators using microarray technology as part of the Diabetes Genome Anatomy Project, a large collaborative research initiative involving the Massachusetts Institute of Technology, University of Massachusetts Medical School, Children’s Hospital Boston and Dana-Farber Cancer Institute.

Future research is also planned in pharmacogenetics, the study of genetic variations in drug response. Dr. Doria hopes that the results of this research will allow healthcare providers to choose the best medications for individual patients based on their genetic profiles.

Selected References
Zhang YY, Gottardo L, Mlynarski W, Frazier W, Nolan D, Duffy J, Marescotti MC, Gervino EV, Johnstone MT, Mantzoros CS, Avogaro A, Doria A. Genetic variability at the leptin receptor (LEPR) locus is a determinant of plasma fibrinogen and C-reactive protein levels.  Atherosclerosis, in press.
 
Ma X, Bacci S, Mlynarski W, Gottardo L, Soccio T, Menzaghi C, Iori E, Lager RA, Shroff AR, Gervino EV, Nesto RW, Johnstone MT, Abumrad NA, Avogaro A, Trischitta V, Doria A.  A common haplotype at the CD36 locus is associated with high free fatty acid levels and increased cardiovascular risk in Caucasians. Hum Mol Genet 13:2197-2205, 2004.

Kim SH, Ma X, Weremowicz S, Ercolino T, Powers C, Mlynarski W, Bashan KA, Warram JH, Mychaleckyj J, Rich SS, Krolewski AS, Doria A.  Identification of a locus for maturity-onset diabetes of the young (MODY) on chromosome 8p23.  Diabetes 53:1375-1384, 2004.

Kim SH, Ma X, Klupa T, Powers C, Pezzolesi M, Warram JH, Rich SS, Krolewski AS, Doria A. Genetic modifiers of the age at diagnosis of diabetes (MODY3) in carriers of hepatocyte nuclear factor-1a mutations map to chromosomes 5p15, 9q22, and 14q24. Diabetes 52:2182-2186, 2003.

Menzaghi C, Ercolino T, Di Paola R, Berg AH, Warram JH, Scherer PE, Trischitta V, Doria A. A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. Diabetes 51:2306-2312, 2002.