Dianna M. Milewicz, M.D., Ph.D.
July 1, 2014
President George H.W. Bush Chair of Cardiovascular Medicine
Director of the Division of Medical Genetics
Professor and Vice-Chair of the Department of Internal Medicine
The University of Texas Health Science Center at Houston, TX
Research in the Milewicz laboratory has three components. The first component is recruiting and clinically characterizing families with multiple members with vascular disease, including thoracic aortic aneurysms, acute aortic dissections, cerebral aneurysms, and early onset ischemic strokes. The second component is focused on identifying genes causing familial vascular disease and identifying the defective gene at mapped loci. Finally, the third component uses cell biology and mouse models to understand how defective genes alter smooth muscle cell function. The lab identified mutations in ACTA2 as a cause of diffuse and diverse vascular disease, an example of how these three components work together. ACTA2 mutations were initially identified in families with autosomal dominant inheritance of thoracic aortic aneurysms and dissections. Through clinical assessment of the families with ACTA2 mutations and review of the aortic pathology, it was determined that ACTA2 mutations also caused early onset occlusive diseases, including coronary artery disease and stroke. A mouse of model of these ACTA2 mutations has been established to determine how mutations in one gene can lead to both enlargement and occlusion of arteries.
Find more information on the web: https://med.uth.edu/im/divisions/medical-genetics/
Andrew Peters: Graduate student (MD/PhD)
Ping Zhou: Graduate student (PhD)
Gregory Aird: Undergraduate student
Eileen Brady: Undergraduate student
Dr. Shanzi Wang: Postdoctoral Fellow
Dr. Jiyuan Chen: Senior Research Associate
Dr. Xue-Yan Duan: Senior Research Assistant
Zhao Ren: Research Assistant
Dr. Shao-Qing Kuang: Assistant Professor
Dr. Limin Gong: Assistant Professor
Dr. Dongchuan Guo: Associate Professor
Ellen Regalado: Assistant Professor, Genetic Counselor
Alana Cecchi: Instructor, Genetic Counselor
Dr. Hariyadarshi Pannu, Program Manager
- Boileau C, Guo D-C, Hanna N, Regalado ES, Detaint D, Gong L, Varret M, Prakash S, Li AH, d'Indy H, Braverman AC, Grandchamp B, Kwartler CS, Gouya L, Santos-Cortez RLP, Abifadel M, Leal SM, Muti C, Shendure J, Gross M-S, Rieder MJ, Vahanian A, Nickerson DA, Michel JP, NHLBI Go Exome Sequencing Project, Jondeau G, Milewicz DM. TGFB2 loss of function mutations cause familial thoracic aortic aneurysms and acute aortic dissections associated with mild systemic features of the Marfan syndrome. Nature Genetics 2012 Aug; 44(8):916-921.
- Kuang S-Q, Geng L, Prakash SK, Cao J-M, Guo S, Villamizar C, Kwartler CS, Peters AM, Brasier AR, Milewicz DM. Aortic Remodeling After Transverse Aortic Constriction in Mice is Attenuated with AT1 Receptor Blockade. Arterioscler Thromb Vasc Biol. 2013 Sep; 33(9):2172-9.
- Guo DC, Regalado E, Casteel DE, Santos-Cortez RL, Gong L, Kim JJ, et al. Recurrent Gain-of-Function Mutation in PRKG1 Causes Thoracic Aortic Aneurysms and Acute Aortic Dissections. Am J Hum Genet 2013;93(2):398-404.
- Kwartler CS, Chen J, Thakur D, Li S, Baskin K, Wang S, et al. Overexpression of smooth muscle myosin heavy chain leads to activation of the unfolded protein response and autophagic turnover of thick filament associated proteins in vascular smooth muscle cells. J Biol Chem 2014; 289: 14075-14088.
- Humphrey JD, Milewicz DM, Tellides G, Schwartz MA. Dysfunctional mechanosensing in aneurysms. Science 2014;344(6183):477-9.
The John Ritter Foundation for Aortic Health http://johnritterfoundation.org/
John Ritter Research Program in Aortic and Vascular Disease http://www.johnritterresearchprogram.org/
Thoracic Aortic Disease Coalition http://www.tadcoalition.org/tad/
The Marfan Foundation http://www.marfan.org/
EDS Network http://www.ehlersdanlosnetwork.org/
Montalcino Aortic Consortium (MAC)
- Cardiology Grand Rounds at Yale School of Medicine, New Haven, CT, 12/13.
- Ida M. Green Distinguished Visiting Professor Honoring Women in Science, University of Texas Southwestern Medical School, Dallas, TX, 2/14.
Scientia potentia est