Elgavish2rev2Associate Professor of Medicine
Program Manager, Program in Immunology

 
Address: 

Shelby Building, Room 415
1825 University Boulevard
35294-2182

Telephone:(205) 934-6547
Email: aelgavis@uab.edu

 

Education

BS, Tel Aviv University, Tel Aviv, Israel
MSc, Tel Aviv University, Tel Aviv, Israel
PhD, Wezimann Institute of Science, Rehovoth, Israel
Fogarty Visiting Fellow, Laboratory of Membrane Biology, NIH

 

Awards

Fogarty Fellowship, NIH, 1979-1981

American Lung Association, Career Investigator Award, 1987-1992

 

Research Interests

My main scientific interests have been in the biology of the genitourinary tract. Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) is a chronic inflammatory disease of the bladder wall. More than 100 years after first being described, the diagnosis of BPS/IC is still associated with controversy. Given the difficulties associated with the diagnosis of BPS/IC, it is not surprising that the etiology of this syndrome is poorly understood. Several theories for the etiology of BPS/IC have been proposed over the years including infection, immunological etiology, leaky urothelium resulting from a deficiency of its surface coat of glycosaminoglycans, activated mast cells and neural changes.

In vitro studies in my laboratory have been consistent with the possibility that BPS/IC may develop in response to noxious stimuli in the bladder lumen. Thus, lipoteichoic acid (LT-2), a cell wall component of the gram-positive bacterium Streptococcus faecalis, stimulated the proliferation rate of a subpopulation of basal uroepithelial cells with high proliferative potential (possibly stem cells). their progeny differentiated at a higher rate and displayed abnormal expression and cellular distribution of β1 integrins, and LT-2 required activation of iNOS and NFκB. Moreover, our studies provided evidence for altered proliferative ability of progenitors of urothelial cells in cell cultures isolated from patients with BPS/IC. These studies raised a number of questions: What are the mechanisms by which noxious stimuli in the bladder lumen may trigger abnormal function of the muscle and nerve tissue underlying the uroepithelium, causing pain and persistent urge to void? In addition, how is it possible that chronic symptoms similar to those characteristic of bacterial cystitis persist for years in patients with BPS/IC in whom no infectious agent is detected at the time of diagnosis? Based on emerging data from several laboratories, I postulated in a recent review that epigenetic reprogramming mechanisms in the bladder may provide an explanation for uroepithelial, mast cells and nerve cell abnormalities in BPS/IC, as well as propagation of this altered state in the absence of the signal that may have triggered it. Data supporting this hypothesis would provide a rationale for new diagnostic, treatment and dietary intervention options for BPS/IC.

My second scientific interest is dietary prevention of prostate cancer (PC). PC is the most commonly diagnosed cancer in North American men. Findings of latent or clinically insignificant PC occurs in a large proportion, and at equal rates, in autopsy studies among men from Asian countries and the United States. In contrast, the incidence of clinically significant PC is an order of magnitude higher in the United States. Epidemiological studies suggest that this might be attributable to differences in environmental factors and life style, including nutrition. Aggressive PC is less prevalent among Asian men where the intake of soy products is very high. However, with Westernization and loss of traditional eating habits, the pattern of disease incidence is also changing in Asian men. On the basis of these findings, it has been postulated that phytoestrogens, including genistein, may have a preventive role in PC. Studies in my laboratory in a transgenic mouse model of prostate cancer (TRAMP mice), supported this hypothesis

Prostate cancer fatalities are rarely due to primary tumors, but rather to widespread metastatic disease. The preferential colonization of bone by prostatic adenocarcinomas has been attributed to the passage of prostate epithelial cells from the prostate to the spine via paravertebral blood vessels. However, molecular mechanisms that facilitate retention of metastatic cells in bone and, their subsequent unrestricted proliferation, are poorly understood. In my laboratory, in vitro studies in cell cultures isolated from the human prostate and in vivo studies in the  transgenic mouse model of prostate cancer focused on cell adhesion-mediated molecular mechanisms that: (i) May underlie progression of slow growing prostate tumors to metastatic growth; and that (ii) May be the target of preventive strategies that delay progression of indolent prostate tumors to metastatic growth.

More recent collaborative studies with Gabriel A. Elgavish were focused on developing an MRI method for early noninvasive detection of developing PC.

In the past few years, in collaborative studies with Harry W. Schroeder, Jr., my interests have expanded to the link between natural protection, e.g., against pneumococci, and D(H) gene conservation.

 

Publications

Click here for a complete list of publications. Below are a few selected papers


Mohamed Khass, Robert L. Schelonka, Cun Ren Liu, Ada Elgavish, Laurence Morel, Peter D. Burrows, Harry W. Schroeder, Jr. 2017. Alterations in B cell development, CDR-H3 repertoire and dsDNA-binding antibody production among C57BL/6 ΔD−iD mice congenic for the lupus susceptibility loci sle1, sle2 or sle3. Autoimmunity 50: 42-51.


Wang Y, Hwangpo T, Martin MP, Vince N, Qi Y, Reynolds RJ 4th, Absher D, Gao X, Ballinger CA, Burrows PD, Atkinson TP, Brown EE, Elgavish A, Liu C, Carrington M, Schroeder HW. 2016. Killer cell immunoglobulin-like receptors are associated with common variable immune deficiency pathogenesis. J Allergy Clin Immunol. 138(5):1495-1498. PMID: 27665490


Yuge Wang, Pratibha Kapoor, Robert Parks, Aaron Silva-Sanchez, S. Munir Alam, Laurent Verkoczy, Hua-Xin Liao, Yingxin Zhuang, Peter Burrows, Michael Levinson, Ada Elgavish, Xiangqin Cui, Barton F. Haynes and Harry Schroeder Jr. 2016. HIV-1 gp140 epitope recognition is influenced by immunoglobulin DH gene segment sequence. Immunogenetics. 68(2):145-55. PMID: 26687685 PMCID: PMC4729650


Silva-Sanchez A, Liu CR, Vale AM, Khass M, Kapoor P, Elgavish A, Ivanov II, Ippolito GC, Schelonka RL, Schoeb TR, Burrows PD, Schroeder HW Jr. 2015. Violation of an Evolutionarily Conserved Immunoglobulin Diversity Gene Sequence Preference Promotes Production of dsDNA-Specific IgG Antibodies. PLoS One. 10(2):e0118171. PMID: 25706374 PMCID: PMC4338297


Vale AM, Kapoor P, Skibinski GA, Elgavish A, Mahmoud TI, Zemlin C, Zemlin M, Burrows PD, Nobrega A, Kearney JF, Briles DE, Schroeder HW Jr. 2013. The link between antibodies to OxLDL and natural protection against pneumococci depends on D(H) gene conservation. J Exp Med. 210(5):875-90. PMID: 23589567 PMCID: PMC3646500

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