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Mohamad Azhar Mohamad Azhar, Ph.D.
Associate Professor

Academic Appointments:
Research Assistant Professor, BIO5 Institute, University of Arizona, Tucson, Arizona
Assistant Research Professor, Indiana University School of Medicine, Indianapolis, Indiana

Postdoctoral Training:
University of Cincinnati College of Medicine, Ohio

Education
B.S. Biochemistry (Hons) (1989): Aligarh Muslim University, Aligarh, India
M.S. Biotechnology (1991): Aligarh Muslim University, Aligarh, India
Ph.D. (1997): Developmental Biology & Genetics,
Indian Institute of Science, Bangalore, India

Contact Information:
Office:(803) 216-3831
Lab:(803) 216-3839; (803) 216-3827
Email:mohamad.azhar@uscmed.sc.edu

Research Focus:

My research focus is on gaining an understanding of the unique and redundant biological function and properties of the three transforming growth factor beta (TGFβ) ligands and their signaling mechanisms in cardiovascular development and homeostasis and in disease pathogenesis. Our laboratory uses molecular, biochemical, physiological, pharmacologic (small molecule inhibitors), cell and tissue culture, and combined optical and biomechanical engineering approaches to analyze cell/tissue/organ-specific conditional/inducible gene knockout and transgenic mouse models. Our research is currently funded, in parts, from the National, Health, Lung, and Blood Institute (NHLBI) (R01HL126705).

Cardiovascular disease is the number one cause of death and morbidity in the United States. As a result of improved medical and surgical management of congenital cardiovascular malformations, about 90% of children born with congenital heart diseases now live into neonatal, postnatal and adult stages of life. Genetic mutations/dysregulation affecting Transforming Growth Factor beta (TGFβ) ligands signaling is found in several neonatal, pediatric, and adult patients with cardiovascular complications, including valvular heart disease, cardiomyopathy, cardiac fibrosis, and arterial aneurysms. TGFβ family consists of three multifunctional ligand proteins (TGFβ 1, 2, 3). Our overall objective is to determine the mechanisms by which TGFβ ligands regulate cardiovascular development and maintain the cardiovascular structure and function at neonatal, postnatal and adult stages. The long term goal also includes an investigation into the role of the three TGFβ ligands in the susceptibility, onset, and progression of adult cardiovascular diseases. A striking number of cardiovascular defects of humans are modeled in mice with mutation(s) in one or more genes encoding TGFβ ligands. Thus, delineating TGF ligands signaling networks involved in specific aspects of cardiovascular development and cardiovascular structure and function during the aging process should inform novel therapeutic approaches with higher specificity and more limited side effects.


Ongoing projects include:

Project 1: Analysis of TGFbeta ligands function in development and pathogenesis of calcific aortic valve disease (CAVD)

The overall goal is to determine the role and the underlying regulatory mechanisms of TGFβ ligands in vivo in development and pathogenesis of calcific aortic valve disease (CAVD). (Funded by R01HL126705)

Project 2: Role of TGF-beta2 in Congenital Heart Disease (CHD)

The overall goal is to determine the cell-specific role of TGF-beta2 and its downstream mechanisms in development of congenital heart defects and adult aortic and mitral valve disease.

Project 3: Role of TGFbeta Ligand Function in the Development and Pathogenesis of Thoracic Aortic Aneurysms and Dissection (TAAD)

The major goals of this project are to define cell type specific function and mechanisms of TGF-beta2 in development and progression of thoracic aortic aneurysm and dissection.


Teaching:

MCBA D602: Medical Microscopic Anatomy (Medical Student Teaching)

BMSC 708/702: Human Cell and Molecular Biology I

MCBA743-001: Molecular Imaging Methods in Biomedical Research II (Graduate Student Teaching)

Anatomy and Physiology for Biomedical Engineers or Human Cell and Molecular Biology (Undergraduate Teaching)


Grant Study Section:

American Heart Association, Cardiovascular Development Basic Science (CVD BSc) Grant Review Committee


Azhar Lab Members

Our lab consists of postdoctoral fellows, students, and research assistant. Students are from Integrated Biomedical Sciences PhD Program through the University of South Carolina. The laboratory has an outstanding scientific environment which is supported by Instrumentation Resource Facility (IRF), Animal Resource Facility (ARF), and Cell Culture Core.




Selected Publications:

  1. Azhar, M., Ware, S.M. (2016) Genetic and developmental basis of cardiovascular malformations. Clin Perinatol 43(1):39-53. PMID: 26876120
  2. Ishtiaq Ahmed,A.S., Bose,G.C., Huang,L.,and Azhar, M. (2014). Generation of mice carrying a knockout-first and conditional-ready allele of transforming growth factor beta2 gene. Genesis. 52, 817-26. PMID: 24895296.
  3. Doetschman,T. and Azhar,M. (2012). Cardiac-specific inducible and conditional gene targeting in mice. Circ. Res. 110, 1498-1512.
  4. Haskett,D., Doyle,J.J., Gard,C., Chen,H., Ball,C., Estabrook,M.A., Encinas,A.C., Dietz,H.C., Utzinger,U., Vande Geest,J.P., and Azhar,M. (2012). Altered tissue behavior of a non-aneurysmal descending thoracic aorta in the mouse model of Marfan syndrome. Cell Tissue Res. 347, 267-277.
  5. Doetschman,T., Georgieva,T., Li,H., Reed,T.D., Grisham,C., Friel,J., Estabrook,M.A., Gard,C., Sanford,L.P., and Azhar,M. (2012). Generation of mice with a conditional allele for the transforming growth factor beta3 gene. Genesis. 50, 59-66.
  6. Doetschman,T., Barnett,J.V., Runyan,R.B., Camenisch,T.D., Heimark,R.L., Granzier,H.L., Conway,S.J., and Azhar,M. (2012). Transforming growth factor beta signaling in adult cardiovascular diseases and repair. Cell Tissue Res. 347, 203-223.
  7. Azhar,M., Brown,K., Gard,C., Chen,H., Rajan,S., Elliott,D.A., Stevens,M.V., Camenisch,T.D., Conway,S.J., and Doetschman,T. (2011). Transforming growth factor Beta2 is required for valve remodeling during heart development. Dev. Dyn. 240, 2127-2141.
  8. Keyes,J.T., Borowicz,S.M., Rader,J.H., Utzinger,U., Azhar,M., and Vande Geest,J.P. (2011). Design and demonstration of a microbiaxial optomechanical device for multiscale characterization of soft biological tissues with two-photon microscopy. Microsc. Microanal. 17, 167-175.
  9. Keyes,J.T., Haskett,D.G., Utzinger,U., Azhar,M., and Vande Geest,J.P. (2011). Adaptation of a planar microbiaxial optomechanical device for the tubular biaxial microstructural and macroscopic characterization of small vascular tissues. J. Biomech. Eng. 133, 075001.
  10. Azhar M, Wang P-Y, Frugier T, Koishi K, Deng C-X, Noakes PG, McLennan I.S. (2010) Myocardial deletion of Smad4 using a novel α skeletal muscle actin Cre recombinase transgenic mouse causes misalignment of the cardiac outflow tract. International Journal of Biological Sciences. 6(6):546-555
  11. Snider, P., Standley KN, Wang J, Azhar M, Doetschman T, Conway SJ (2009) Origin of Cardiac Fibroblasts and the Role of Periostin Circ. Res. 105(10):934-47.
  12. Liao,S., Newman,G., Azhar,M., Doetschman,T. & Schultz,J.J. (2010) The influence of FGF2 high molecular weight (HMW) isoforms in the development of cardiac ischemia-reperfusion injury. J Mol Cell Cardiol , 48(6):1245-54. PMID: 20116383
  13. Azhar,M., Yin,M., Bommireddy,R., Duffy,J.J., Yang,J., Pawlowski,S.A., Boivin,G.P., Engle,S.J., Sanford,L.P., Grisham,C., Singh,R.R., Babcock,G.F. & Doetschman,T. (2009) Generation of mice with a conditional allele for transforming growth factor beta 1 gene. Genesis. 47:423-431.
  14. Azhar,M., Runyan,R.B., Gard,C., Sanford,L.P., Miller,M.L., Andringa,A., Pawlowski,S., Rajan,S. & Doetschman,T. (2009) Ligand-specific function of transforming growth factor beta in epithelial-mesenchymal transition in heart development. Dev.Dyn. 238(5):431-442. DD ArtPix (p fvi). Journal Cover Page Feature
  15. Azhar,M., Yin,M., Zhou,M., Li,H., Mustafa,M., Nusayr,E., Keenan,J.B., Chen,H., Pawlosky,S., Gard,C., Grisham,C., Sanford,L.P. & Doetschman,T. (2009) Gene targeted ablation of high molecular weight fibroblast growth factor-2. Dev.Dyn. 238:351-357.
  16. Liao,S*., Bodmer,J*., Pietras,D*., Azhar,M.*, Doetschman,T. & Schultz,J.E. (2009) Biological functions of the low and high molecular weight protein isoforms of fibroblast growth factor-2 in cardiovascular development and disease. Dev.Dyn. 238:249-264 (*Co-First Authors)
  17. Saxena,V., Lienesch,D.W., Zhou,M., Bommireddy,R., Azhar,M., Doetschman,T. & Singh,R.R. (2008) Dual Roles of Immunoregulatory Cytokine TGF-{beta} in the Pathogenesis of Autoimmunity-Mediated Organ Damage. J Immunol. 180:1903-1912.
  18. Okunade,G.W., Miller,M.L., Azhar,M., Andringa,A., Sanford,L.P., Doetschman,T., Prasad,V. & Shull,G.E. (2007) Loss of the Atp2c1 secretory pathway Ca(2+)-ATPase (SPCA1) in mice causes Golgi stress, apoptosis, and midgestational death in homozygous embryos and squamous cell tumors in adult heterozygotes. J.Biol.Chem. 282:26517-26527.
  19. Kaiser,S., Park,Y.K., Franklin,J.L., Halberg,R.B., Yu,M., Jessen,W.J., Freudenberg,J., Chen,X., Haigis,K., Jegga,A.G., Kong,S., Sakthivel,B., Xu,H., Reichling,T., Azhar,M., Boivin,G.P., Roberts,R.B., Bissahoyo,A., Gonzales,F., Bloom,G.L., Eschrich,S., Carter,S.L., Aronow,J.E., Kleimeyer,J., Kleimeyer,M., Ramaswamy,V., Settle,S.H., Boone,B., Levy,S., Graff,J.M., Doetschman,T., Groden,J., Dove,W.F., Threadgill,D.W., Yeatman,T.J., Coffey,R.J., Jr. & Aronow,B.J. (2007) Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer. Genome Biol. 8:R131
  20. Jamora,C., Lee,P., Kocieniewski,P., Azhar,M., Hosokawa,R., Chai,Y. & Fuchs,E. (2005) A signaling pathway involving TGF-beta2 and snail in hair follicle morphogenesis. PLoS.Biol. 3:131-143. Journal Cover Page Feature
  21. Molin,D.G., Poelmann,R.E., DeRuiter,M.C., Azhar,M., Doetschman,T. & Gittenberger-de Groot,A.C. (2004) Transforming growth factor beta-SMAD2 signaling regulates aortic arch innervation and development. Circ.Res. 95:1109-1117.
  22. Hardie,W.D., Le Cras,T.D., Jiang,K., Tichelaar,J.W., Azhar,M. & Korfhagen,T.R. (2004) Conditional expression of transforming growth factor-alpha in adult mouse lung causes pulmonary fibrosis. Am.J.Physiol Lung Cell Mol.Physiol. 286:L741-L749
  23. Azhar,M., Schultz,J.E., Grupp,I., Dorn,G.W., Meneton,P., Molin,D.G., Gittenberger-de Groot,A.C. & Doetschman,T. (2003) Transforming growth factor beta in cardiovascular development and function. Cytokine Growth Factor Rev. 14:391-407
  24. Molin,D.G., DeRuiter,M.C., Wisse,L.J., Azhar,M., Doetschman,T., Poelmann,R.E. & Gittenberger-de Groot,A.C. (2002) Altered apoptosis pattern during pharyngeal arch artery remodelling is associated with aortic arch malformations in Tgfbeta2 knock-out mice. Cardiovasc. Res 56:312-322.
  25. Paradis,H., Liu,C., Saika,S., Azhar,M., Doetschman,T., Good,W., Nayak,R., Laver,N., Kao,C., Kao,W. & Gendron,R. (2002) Tubedown-1 in remodeling of the developing vitreal vasculature in vivo and regulation of capillary outgrowth in vitro. Dev.Biol. 249:140
  26. Saika,S., Liu,C.Y., Azhar,M., Sanford,L.P., Doetschman,T., Gendron,R.L., Kao,C.W. & Kao,W.W. (2001) TGFbeta2 in Corneal Morphogenesis during Mouse Embryonic Development. Dev Biol 240 :419-432.
  27. Bartram,U., Molin,D.G., Wisse,L.J., M, Azhar., Sanford,L.P., Doetschman,T., Speer,C.P., Poelmann,R.E. & Gittenberger-de,G.A. (2001) Double-outlet right ventricle and overriding tricuspid valve reflect disturbances of looping, myocardialization, endocardial cushion differentiation, and apoptosis in Tgfb2 knockout mice. Circulation 103:2745-2752.