Department of Pathology and Laboratory Medicine Spring 2015 Seminar Series: Friday, February 6,
Kazem Azadzoi, M.D, M.A.
- Professor of Pathology (BU Medical School)
- Professor of Urology (BU Medical School)
- Director of Urology Research (VA Boston Healthcare System)
- Senior Health Scientist (VA Boston Healthcare System)
Bulding 1A, Room 315
150 S. Huntington Ave
Boston, MA 01230
Membership in Professional Organizations
- American Urological Association (AUA), 91-
- International Continence Society (ICS), 95 -
- Society of Urodynamics and Female Urology (SUFU), 10 -
- North-East Smooth Muscle Society, 01 -
- Oxygen Club of California, 96 -
- Society of Basic Urology Research (SBUR), 05 - 09
- National Bladder Foundation (NBF), 99 - 05
- International Society for Sexual Medicine (ISSM), 92 -
Awards and Honors
- Jean-Francois Ginestié Prize for basic research on Erectile Dysfunction, 1990.
- Endourological Society Prize for basic research in Endourology, 1993.
- Jean-Francois Ginestié Prize for basic research on female Sexual Dysfunction, 1996.
- Jack Lapides Prize for basic research in Urodynamic and Neurourology, 1988.
- American Urological Association CIRCON Prize for basic research on Prostatic Disorder, 2000.
- Hall of Fame, Appointed to the International Continence Society Hall of Fame in 2005.
- National Register’s Who’s who in Executives and Professionals, included in the 2005 edition.
- VIP, global Who’s Who, included in the 2007 edition.
- Who’s Who in America, included in the Marquis Who’s Who in America, 2008 edition.
- The Journal of Urology Best reviewer in 2011 Award, 2012.
- Certificate of Appreciation for contribution to Merit Review Program, VA Central Office, 2012.
- Section Editor, Oxidants and Antioxidants in Medical Sciences, 12 -
- Section Editor, Scientifica – Urology, 12 -
- Editorial Board Member, British Journal of Urology International (BJUI), 04 -
- Editorial Board Member, Open Access Journal of Urology, 08 -
- Editorial Board Member, The Scientific World Journal (TSWJ), 11 -
- Editorial Board Member, World Journal of Clinical Urology (WJCU), 11 -
- Editorial Board Member, Journal of Biochemical and Pharmacological Research (JBPR), 12 -
Peer Review Boards & Institutional Committees
- Review board member, VA Surgery Study Section, 08-11
- Review board member, VA Middleton & Barnwell Awards for clinical & basic research, 2012
- Ad hoc reviewer, NIH, Urologic and Kidney Disease Study Section, 2003
- Ad hoc reviewer, NIH, Clinical Sciences Special Emphasis Panel, Urology Section, 1999
- Ad hoc reviewer, NIH, Surgery, Anesthesiology and Trauma (SAT) study section, 1995
- Member, VA Boston Healthcare System Steering Committee, 06-08
- Member, Boston University promotion committee, 2005
- Member, Boston University promotion committee, 2007
- Member, Boston University faculty network for studies of sexual dysfunction, 2008 -
- Member, Boston University faculty network for women studies, gender, and sexuality, 2010 -
- Chairman, VA Boston Health Care System IACUC, 06-08
- Chair Elect, VA Boston Health Care System IACUC, 2012
- Member, Chief of Urology Search Committee, VA Boston Healthcare System, 2012
- American Journal of Urology, 1990 -
- International J. of Impotence Research. 1990 -
- American Journal of Physiology, 1997 -
- Urology (The Gold Journal), 1992 -
- Journal of Neurourology and Urodynamic, 1992 -
- Journal of Andrology, 03 -
- European Urology, 03 -
- Asian J. of Andrology, 03 -
- Molecular and Cellular Biochemistry, 07 -
- Journal of Sexual Medicine, 07 -
- European Surgical Research, 08 -
- European Journal of Obstetrics & Gynecology 2010 -
- Oxidants and Antioxidants in Medicine, 2011 -
Dr. Azadzoi’s research is focused on the role of hypoxia and oxidative stress in simultaneous development of lower urinary tract symptoms (LUTS) and penile erectile dysfunction (ED). The goal is to demonstrate that pelvic ischemia may be an independent factor in aging-associated bladder overactivity and ED. Overactive bladder incorporates to a variety of lower urinary tract symptoms including urinary frequency, urge incontinence, nocturia and pelvic pain. A majority of male patients seen at the urology outpatient clinics for treatment of LUTS also complain of ED. The etiology of bladder overactivity and the close association between LUTS and ED are poorly understood. It is known, however, that most patients with ED-associated LUTS have vascular risk factors such as hypercholesterolemia, atherosclerosis, hypertension and diabetes. These conditions are known to generate reactive oxygen species (ROS) such as superoxide, hydrogen peroxide (H2O2), hydroxyl radicals and nitrosative products that contribute to oxidative tissue injury.
Our clinical studies have shown that changes in human pelvic blood flow correlates with LUTS and ED and that human bladder non-compliance correlates with decreased bladder perfusion. We have developed an experimental model of pelvic atherosclerosis and a computerized cell culture oxycycler system to explore molecular mechanisms and subcellular changes of the ischemic genitourinary system. Our studies suggest that oxidative stress under the ischemic conditions triggers a cascade of molecular events involving oxidative stress-responsive genes, antioxidant defense system, growth factors, and subcellular reactions involving mitochondria and endoplasmic reticulum (ER) stress proteins. Molecular responses involving HIF, TGF-beta, VEGF and NGF were associated with mitochondrial injury, microvasculature damage, neurodegeneration, and fibrosis in the ischemic bladder, prostate and penile erectile tissues. These reactions to oxidative stress impaired the novel pathway of penile smooth muscle relaxation and erection, the NO-cGMP pathway. Treatment with antioxidants appeared to delay or prevent these changes.
Our studies with cultured cells in a computerized oxycycler system showed that human bladder smooth muscle cells are highly reactive to nonconforming oxygen tension. Lipid peroxidation was found in cell hypoxia and oxidative stress while protein oxidation was evident in oxidative stress only. Cell antioxidant capacity decreased in oxidative stress but remained unchanged in hypoxia. Oxidative products were present in cell oxidative stress only while nitrosative products increased in both hypoxia and oxidative stress conditions. Thickened deformed cell membrane, swollen mitochondria and enlarged ER were found in cell hypoxia. Partially lost cell membrane with increased caveolae, swollen mitochondria with degraded cristae, splintered ER, and increased lysosomes were evident in cell oxidative stress. Human bladder smooth muscle cells reactions to hypoxia were consistent with cell survival signaling, possibly to cope with lack of oxygen and energy demand. Changes after cell exposure to oxidative stress were characterized by extensive cell damage and deterioration of the subcellular elements. Mitochondria, ER and lysosomes appeared to mediate bladder smooth muscle cell reactions to hypoxia and free radical incursion. These observations suggest that dysfunctional antioxidant defense system and disruption of the cell organelles may be central to smooth muscle cell degeneration in bladder conditions involving ischemia and oxidative stress.
Kazem Azadzoi, M.D., M.A. (Director)
Mike Siroky, M.D. (Investigator)
Jinghua Yang, Ph.D. (Investigator)
Kimberly Leite-Morris, Ph.D. (Investigator)
Lori Lerner, M.D. (Collaborator)
Subbaroa Yalla, M.D. (Collaborator)
Maryrose Sullivan, Ph.D. (Collaborator)
Vivian Cristofaro, Ph.D. (Collaborator)
Abdulmaged Traish, Ph.D. (Consultant)
Farzana Nipa (Research Assistant)
Yedan Li (Research Assistant)
We are seeking post-doctoral fellows and research assistants to join our investigators at the VA Boston Healthcare System research laboratories. Applicants should email their CVs to Dr. Azadzoi (email@example.com).
- Azadzoi KM, Yalla SV and Siroky MB: Human bladder smooth muscle damage in disturbed oxygen tension. Urology 78: 967e9 – 967e15, 2011.
- Azadzoi KM, Chen B, Radisavljevic ZM, and Siroky Mike: “Molecular Reactions and Ultrastructural Damage in the Ischemic Bladder. J Urology 186: 2115-2122, 2011.
- Zhang Q, Radisavljevic ZM, Siroky MB and Azadzoi KM: Dietary antioxidants improve arteriogenic erectile dysfunction. Int J Andrology 34: 225-235, 2011.
- Azadzoi KM, Golabek T, Radisavljevic ZM, Yalla SV and Siroky MB: Oxidative Stress and Neurodegeneration in penile ischemia. British J Urology 105: 404-410, 2010.
- Azadzoi KM and Siroky MB: Neurologic factors in female sexual function and dysfunction. KJ Urology 51(7): 443-9, 2010.
- Azadzoi KM, Radisavljevic ZM, Golabek T, Yalla SV and Siroky MB: Oxidative modification of mitochondrial integrity and nerve fiber density in the ischemic overactive bladder. J Urology 183 (1):362-369, 2010.
- Azadzoi KM and Siroky MB: Oxidative stress and molecular reactions in arteriogenic erectile dysfunction. Chonn Medical Journal 45: 1-8, 2009.
- Azadzoi KM, Radisavljevic ZM and Siroky MB: Effects of ischemia on tachykinin containing nerves and neurokinin receptors in the bladder. Urology 71(5): 979-83, 2008.
- Azadzoi KM, Yalla SV and Siroky MB: Oxidative stress and neurodegeneration in the ischemic overactive bladder. J Urology 178: 710-715, 2007.
- Azadzoi KM, Master TA and Siroky MB: Effects of chronic ischemia on constitutive and inducible nitric oxide synthase in erectile tissue. J. Andrology 25(3): 382-388, 2004.
- Kim N, Azadzoi KM, and Goldstein I: A nitric oxide-like factor mediates neurogenic relaxation of penile smooth muscle. J Clinical Investigation (JCI) 88: 112-118, 1991.
- Saenz de Tejada I, Goldstein I, Azadzoi KM, Krane RJ and Cohen RA: Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. The New England Journal of Medicine. 320: 1025-1030, 1989.
- Goldstein I, Saenz de Tejada I, Azadzoi KM, and Payton T: Neurogenic Impotence: A Pharmacologic Approach. In “Contemporary Management of impotence”: 147-166, 1988.
- Siroky MB and Azadzoi KM: Male and Female Sexual Dysfunction. In “Pelvic Floor Disorders” WB Saunders: 89-120, 2004.
- Azadzoi KM: Effect of chronic ischemia on bladder structure and function. In “Bladder Disease: Research concepts and clinical applications”: 271-280, 2004.
- Azadzoi KM and Siroky MB. Neurogenic Sexual Dysfunction in Men and Women. In Male Sexual Function: A Guide to Clinical Management: 195-226, 2006.