Research interests include differential effects of sepsis on immune cell function, the role of programmed cell death/apoptosis in immune dysfunction observed following hemorrhage and/or sepsis, as well as the contribution of the apoptotic process to phagocyte mediated acute lung injury resultant from shock and/or septic insults.

Biography

Dr. Ayala is Professor of Surgery (Research) at R.I Hospital/Brown University School of Medicine. He serves/ served as both a standing and an ad hoc member of the NIH SAT-Study Section, various NIH site visit teams, as well as served on the VA-DoD Merit Review Board. He has been recognized by his peers through election to President (04-05), Treasurer (02-04), and Sci Program Chair (01) of the Shock Society and as selection as Recorder/Exec Council (05-07) of the Surgical Infection Society. Dr. Ayala was also the recipient of the Shock Society's 10th annual 'Scientific Achievement Award' (07). He has over 250 manuscripts/review articles to his credit and is funded by the NIH. He is also a member of the training faculty of the Brown University Graduate Pathobiology Program and is and adjunct Professor/mentor in the Univ. R.I. graduate program in the Department of Cell. & Mol Biol During his tenure at Brown Univ. and previously at Mich St Univ he has had the privilege of mentoring students ranging from undergraduates and medical students to residents and post-doctoral fellows.

Institutions

RIH

Research Description

The work in our laboratory has centered on understanding the patho-physiological effects of shock/tissue injury/sepsis that lead to immune dysfunction and subsequent multiple organ failure in the critically ill trauma patient. We have described, over the years, numerous deficits in both components of cell-mediated (T-cell/NK-T cell/B-cell) and innate (macrophage, neutrophil, dendritic cells) immune responsiveness induced by shock or sepsis, which are underpinned by alterations in cell signaling, protein translation, and transcription patterns. Particular emphasis has been directed at defining the role of soluble mediators (e.g., IL-4, IL-10, TGF-b, PGE2, NO, steroids, etc.), inhibitory receptors (e.g., PD-1:PD-L1/L2, CTLA-4, FasL:Fas, etc.) and/or cellular pathways (e.g., p38 MAPKs, STAT 1/4/6, SOCS 1/3, Shp1/2, NFkB, etc.) involved in orchestrating these changes in mouse models. We have also found evidence of alterations of the immune cell's apoptotic process, present in these animals, and are actively examining the contribution of this pathway. It is our hope that, by understanding the cellular/molecular mechanisms which control these alterations in the traumatized or septic animal/patient, we will improve our ability to treat them.

Major Theme of Research: Immunology and infection


Laboratory Staff-Contact List (Rev: 9/03/2009):


Xin Huang, Ph.D., M.D.
Research Associate
Aldrich 242
401-444-6706
XHuang@lifespan.org

Gwendolyn Elphick, Ph.D., M.S.
Research Associate
Middle House 211
401-444-4587
GElphick@lifespan.org

Rajan Thakkar, M.D.
Armand D. Versaci Res. Scholar/
Surgical Resident
Aldrich 226
401-444-6482
Rajan_Thakkar@brown.edu

Sean Monaghan, M.D.
Armand D. Versaci Res. Scholar/
Surgical Resident
Aldrich 242
401-444-6706
Sean_Monaghan@brown.edu



Graduate Students:


Sam McNeal, B.S.
Grad. Student
(Brown U-Pathobiol. Prog.)
Aldrich 226
401-444-6482
Sam_McNeal@brown.edu

Noelle A. Hutchins, B.S.
Grad. Student / NRSA pre-doc fellow
(Brown U-Pathobiol. Prog.)
Aldrich 228
401-444-6728
Noelle_Hutchins@brown.edu

Nicholas Shubin, B.S.
Grad. Student
(Brown U-Pathobiol. Prog.)
Aldrich 226
401-444-6482
Nicholas_Shubin@brown.edu



Research Assistants:


Yaping Chen, B.S.
Sr. Res. Assist.
Aldrich 228
401-444-6728
Ychen2@lifespan.org



Administrative:


Courtney V. Coto, A.D. Med. Trans.
Admin. Assistant
Aldrich 230
401-444-5157
CCoto@lifespan.org



Undergraduate/Medical Students:


Yvonne Wong, B.S.
Brown U. Med. Student-Independent Study
Aldrich 223
401-444-4711
Yvonne_Wong@brown.edu

Sima Patel
Brown U. undergrad. student-Independent Study
Aldrich 238
401-444-7101
Sima_Patel@brown.edu

Nicholas Carter, B.A.
Brown U. Med. Student-Independent Study
Aldrich 238
401-444-4-7101
Nicholas_Carter@brown.edu



Laboratory Alumni (back to: 2000):


Sadella Santos.

Fabienne Venet, Ph.D., M.S., Pharm.D.

Arnaldo Carriera

Ana Moreno, B.S.

Megan Garber, B.S., M.S.

Earl Campbell, III

Brian J. Horner, D.O.

Ryan Swan, M.D.

Doreen Wesche-Soldato, Ph.D.

Leia Foster

Caroline Hu, B.A., M.S.

Mario Perl, M.D.

Ulrike (Uli) Perl, R.N.

Antonio Funches, B.S.

Tina Rachel, B.A., M.S.

Nicholas Winoski, B.A.

Ben Galen, B.S.

Lesley Doughty, M.D.

Rani Cooma-Ramberan, B.S.

Leslie Jones, B.S.


Sarah Newton (maiden name: Bray), B.A.

Rebecca Rhee, B.A., M.D.

Yanli Ding, D.D.S., Ph.D, D.M.D

Patricia S. Grutkoski, Ph.D.

Crystal Lane, B.S.

Grace Jarrar (maiden name: Song), M.D., B.A.

Lara Watkins, B.A.

Amit R.T. Joshi, M.D., B.A.

Rory A. Priester, M.D., B.A.

Awards

Recipient of the Shock Society's - Scientific Achievement Award (2007)

Surgical Infection Society - Joseph Susman Awarde (1994)

selected as:
SIS Recorder/Council Member (2005-07)

Elected as:
Shock Society- President (2004-05), Treasurer (2002-04), Sci. Program Chair. (2001)

Affiliations

American Society of Investigative Pathology
American Association for the Advancement of Science
American Association of Immunologists
International Cytokine Society
Michigan Society for Medical Research
Society of Protozoologists
Shock Society
Surgical Infection Society
Society of Critical Care Medicine
Society of Leukocyte Biology

Funded Research

Active Grant Support:

2003-2012
NIH-NIHLBI: "Regulatory Mechanisms of Acute Lung Injury: Phagocyte Apoptosis."
Grant No. 2 RO1 HL63898-06
Principal Investigator: Alfred Ayala
Total Support = $1,542,875 in direct and indirect cost (for 2008-2012).

1991-2012
NIH-NIGMS Research Grant: "Differential Effects of Sepsis on Macrophage Function."
Grant No. 3 R01 GM46354-15
Principal Investigator: Alfred Ayala
Total Support = $1,331,926 in direct and indirect cost (for 2008-2012).

1999-2009
NIH-NIGMS Research Grant: "Programmed Cell Death: Role in Septic Immune Suppression."
Grant No. 3 RO1 GM53209-15 (on no cost extension).
Principal Investigator: Alfred Ayala
Total Support = $1,106,943 in direct and indirect cost (for 2004-2008)

2004-2009
NIH-NIGMS: "Trauma-inflammation Research Training."
Grant No. T32-GM08768
Program Director: Jorge E. Albina
Co-Director/Executive Committee/Faculty: Alfred Ayala
Total Support Requested = $1,201,764 in direct and indirect cost.

2003-2009
NIH-Research Grant: "Neutrophil-Kupffer Cell Interaction during Infection."
Grant No.: R01-DK 61511
Principle Investigator: Stephen H. Gregory
Collaborator: Alfred Ayala
Total Support Requested = ~$1,250,000 in direct and indirect cost.

2001-2010
NIH-NIHLBI: "Short-term Training for Minority Students."
Grant No. T35-HL67704
Principal Investigator: Sharon I.S. Rounds
Faculty Trainer: Alfred Ayala
Total Support = $229,900 in direct and indirect cost.

Courses Taught

• Dir. Res./Grad. Independent Study (Bio296)
• Intro. to Pathobiol. Res.-overview lect. (Bio285)
• Med. Student Independent Study (Bio710)
• Reading Sci Pubs (IMSD Training Module-Fall 2009)
• Topics in Pathiobiology: Immunopathology (Bio284)
• Undergrad. Independent Study (Bio 195/196)

View My Full Publication List in pdf format

Selected Publications

• Venet, F., Chung, C.S., Huang, X., Lomas-Neira, J., Chen, Y., Ayala, A. 2009. Indirect lung injury: a role for regulatory T lymphocytes in the development of pulmonary inflammation. J. Immunol. 183:3472-80 (PMID: 19641139). (2009)
• Huang, X., Venet, F., Wang, Y.L., Lepape, A., Yuan, Z., Wang, Y.L., Chen, Y., Swan, R., Kherouf, H., Monneret, G., Chung, C.S., Ayala, A. 2009. PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis. Proc. Natl. Aacd. Sci. U.S.A. 106:6303-6308 (PMID: 19332785) (2009)
• Elphick, G., Sarangi, P., Hyun, Y-M., Hollenbaugh, J., Ayala, A., Biffl, W., Chung, H-L., Rezaie, A., McGarth, J., Topham, D., Reichner, J., Kim, M. 2009. Recombinant human activated protein C inhibits integrin-mediated neutrophil migration. Blood 113:4078-4085. (PMID: 19244161) (2009)
• Hu, C.*, Venet, F.*, Heffernen, D.S., Wang, Y., Horner, B., Huang, X., Chung, C.S., Gregory, S.H., Ayala, A. 2009. The role of hepatic invariant (i)NKT cells in systemic/ local inflammation and mortality during polymicrobial septic shock? J. Immunol. 182(4):2467-75.(*C.K.H and F.V. contributed equally as first authors to this work) (PMID: 19201902).(2009)
• Fritzell, Jr., J.A., Mao, Q, Gundavarapu, S., Pasquariello, T., Aliotta, J., Ayala, A., Padbury, J.F., De Paepe, M.E. 2009. Fate and effects of adult bone marrow cells in lungs of normoxic and hyperoxic newborn mice. Amer. J. Resp. Cell Mol. 40:575-587 (PMID: 18988921).(2009)
• Stromberg, P., Woolsey, C., Clark, A., Clark, J., Turnbull, I., McConnell, K., Chang, K., Chung, C-S., Ayala, A., Buchman, T., Hotchkiss, R.S., Coopersmith, C. 2009. CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis. FASEB J. 23:1817-1825 (PMID: 19158156) (2009)
• Lomas-Neira, J., Chung, C.S., Ayala, A. 2008. RNA interference as a potential therapeutic treatment for inflammation associated lung injury. Inter. J. Clin. Exp. Med. 1:154-160 (REVIEW; PMID: 19079669).(2008)
• Perl, M., Lomas-Neira, J., Chung, C.S., Ayala, A. 2008. Epithelial apoptosis and neutrophil recruitment in acute lung injury - A unifying hypothesis? What we have learned from small interfering RNAs. Mol. Med. 14:465-475 (REVIEW; PMID: 18368145).(2008)
• Venet, F., Chung, C.S., Monneret, G., Huang, X., Horner, B., Garber, M.E., Ayala, A. 2008. T-regulatory cell populations in trauma and sepsis. J. Leuko. Biol. 83:523-535 (REVIEW; PMID: 17913974).(2008)
• Wesche-Soldato, D.E., Lomas-Neira, J., Perl. M., Chung, C.S., Ayala, A. 2008. Hydrodynamic delivery of siRNA in a mouse model of sepsis. Methods Mol Biol. 442:67-73 (PMID: 18369778).(2008)
• Venet, F., Tissot, S., Debard, A-L., Faudot, Crampe, A., Pachot, A., Ayala, A., Monneret, G. 2007. Decreased monocyte human leukocyte antigen-DR expression after severe burn injury: correlation with severity and secondary septic shock. Crit. Care. Med. 35:1910-1917 (PMID: 17568330).(2007)
• Scumpia, P.O., Delano, M.J., Kelly-Scumpia, K.M., Weinstein, J.S., Wynn, J.L., Xia, C., Winfield, R.D., Chung, C.S., Ayala, A., Heyworth, P.G., Reeves, W.H., Clare-Salzler, M.J., Moldawer, L.L. 2007. Treatment with GITR agonistic antibody corrects adaptive immune dysfunction and improves survival in murine sepsis. Blood 110:3673-3681 (PMID: 17690255).(2007)
• Huang, X., Venet, F., Lomas-Neira, J.L., Chung, C.S., Ayala, A. 2007. Changes in dendritic cell function in the immune response to sepsis. Expert Opin. Biol. Ther. 7:929-938 (REVIEW; PMID: 17665984).(2007)
• Perl, M., Chung, C.S., Perl, U., Lomas-Neira, J.L., De Paepe, M., Cioffi, W.G., Ayala, A. 2007. Fas induced pulmonary apoptosis and inflammation during indirect acute lung injury. Amer. J. Resp. & Crit. Care. Med. 176:591-601 (PMID: 17600273).(2007)
• Swan, R., Chung, C.S., Albina, J.E., Cioffi, W.G., Perl, M., Ayala, A. 2007. Polymicrobial sepsis enhances apoptotic immune cell clearance by splenic macrophages. Surgery 142:253-261 (PMID: 17689693).(2007)
• Chung, C.S., Chen, Y.P., Grutkoski, P.S., Doughty, L.A., Ayala, A. 2007. SOCS-1 is a central mediator of steroid-increased thymocyte apoptosis and decreased survival following sepsis. Apoptosis 12:1143-1153 (PMID: 17380787).(2007)
• Wesche-Soldato, D.E., Chung, C.S., Gregory S. H., Salazar-Mathers, T.P., Ayala, C.A., Ayala, A. 2007. CD8+ T cells promote inflammation and apoptosis in the liver after sepsis: role of Fas-FasL. Amer. J. Pathol. 171:87-96 (PMID: 17478568).(2007)
• Delano, M.J., Scumpia, P.O., Weinstein, J.S., Coco, D., Nagaraj, S., Kelly, K.M., O'Malley, K.M, Wynn, J., Antonenko, S., Al-Quran, S., Swan, R., Chung,C.S., Atkinson, M.A., Ramphal, R., Gabrilovich, D.I., Reeves, W.H., Ayala, A., Phillips, J., LaFace, D., Heyworth, P.G., Clare-Salzler, M., Moldawer, L.L. (2007) MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T-cell suppression and TH2 polarization in polymicrobial sepsis. J. Exp. Med. 204: 1463 – 1474 (PMID: 17548519).(2007)
• Lomas-Neira, J., Chung, C.S., Perl, M., Gregory, S., Biffl, W., Ayala, A. 2006. Role of alveolar macrophage & migrating neutrophils in hemorrhage induced priming for ALI subsequent to septic challenge. Amer. J. Physiol. 290:51-58 (PMID: 16157517).(2006)
• Chung, C.S., Watkins, L., Song, G.Y., Lomas-Neira, J., Cahoone, E.V., Cioffi, W.G., Ayala, A. 2006. Deficiency in gamma-delta T-lymphocytes compromises the ability of mice to survive polymicrobial sepsis. Amer. J. Physiol. 291:R1338-1343 (PMID:16878028).(2006)
• Wesche, D.E., Lomas-Neira, J.L., Perl, M., Chung, C.S., Ayala, A. 2005. Leukocyte apoptosis and its significance in sepsis and shock. J. Leukocyte Biol. 78:325-337 (REVIEW; PMID: 15817707).(2005)
• Perl, M., Chung, C.S., Ayala, A. 2005. Apoptosis. Crit. Care Med.-Supplt. 33:S526-S529 (REVIEW; PMID: 16340441).(2005)
• Lomas-Neira, J.L., Perl, M., Chung, C.S., Ayala, A. 2005. Shock and hemorrhage: An overview of animal models. Shock 24 (Suplt. 1): 33-39 (REVIEW; PMID: 16374370).(2005)
• Wesche-Soldato, D.E., Chung, C.S., Lomas-Neira, J., Doughty, L.A., Gregory S. H., Ayala, A. 2005. In vivo delivery of caspase 8 or FAS siRNA impoves the survival of septic mice. Blood. 106:2295-2301 (PMID: 15941915).(2005)
• Lomas-Neira, J.L., Chung, C.S., Wesche, D.E., Perl, M., Ayala, A. 2005. In vivo gene silencing (with siRNA) of pulmonary expression of MIP-2 vs. KC results in divergent effects on hemorrhage induced neutrophil mediated septic acute lung injury. J. Leukocyte Biol. 77:846-853 (PMID: 15695553).(2005)
• Song, G.Y., Chung, C.S., Cioffi, W.G., Ayala, A. 2005. Insights into the contribution of STAT4 and STAT6 signaling to the morbidity seen in a low-mortality model of sepsis. Intensive Care Med. 31:1564-1569 (PMID: 16172848).(2005)
• Perl, M., Chung, C.S., Lomas-Neira, J., Rachel, T.M., Biffl, W.L., Cioffi, W.G., Ayala, A. 2005. Silencing of Fas- but not caspase-8 in lung epithelial cells ameliorates experimental acute lung injury. Amer. J. Pathol. 167:1545-559 (PMID: 16314469).(2005)
• Ding, Y., Chung, C.S., Bray, S., Chen, Y., Grutkoski, P.S., Carlton, S., Albina, J.E., Ayala, A. 2004. Polymicrobial sepsis induces divergent effects on splenic and peritoneal dendritic cell function in mice. Shock 22:137-144 (PMID: 15257086).(2004)
• Grutkoski, P.S., Chen, Y., Chung, C.S., Cioffi, W.G., Ayala, A. 2004. Putative mechanism of hemorrhage-induced leukocyte hyporesponsiveness: induction of suppressor of cytokine signaling (SOCS)-3. J. Trauma 56:742-748 (PMID: 15187736).(2004)
• Lomas-Neira, J.L., Chung, C.S., Grutkoski, P.S., Miller, E.J., Ayala, A. 2004. CXCR2 inhibition suppresses hemorrhage induced priming for acute lung injury in mice. J. Leukoc. Biol. 76:58-64 (PMID: 15123771).(2004)
• Grutkoski, P.S., Chen, Y., Chung, C.S., Ayala, A. 2003. Sepsis-induced SOCS-3 expression is immunologically restricted to phagocytes. J. Leukoc. Biol. 74:916-922 (PMID: 12960286).(2003)
• Rhee, R.J., Carlton, S., Lomas, J.L., Lane, C., Brossay, L., Ayala, A. 2003. Inhibition of CD1d activation suppresses septic mortality: a role for NK-T cells in septic immune dysfunction. J. Surg. Res. 115:74-81 (PMID: 14572776).(2003)
• Lomas, J.L.,Chung, C.S., Grutkoski, P.S., LeBlanc, B.W., Lavigne, L., Reichner, J., Gregory, S.H., Doughty, L.A., Cioffi, W.G., Ayala, A. 2003. Differential effects of MIP-2 and KC on hemorrhage induced neutrophil priming for lung inflammation: assessment by adoptive cell transfer in mice. Shock 19:358-365 (PMID: 12688548).(2003)
• Chung, C.S., Song, G.Y., Lomas, J., Simms, H.H., Chaudry, I.H., Ayala, A. 2003. Inhibition of Fas/Fas ligand (FasL) signaling during sepsis has tissue specific effects on macrophage apoptotic and functional capacity. J. Leukocyte Biol. 74:344-351 (PMID: 12949237)(2003)
• Ayala, A., Chung, C.S., Lomas, J.L., Song, G.Y., Doughty, L.A., Gregory, S.H., Cioffi,W.G., LeBlanc, B.W., Reichner, J., Simms, H.H., Grutkoski, P.S. 2002. Shock induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency. Amer. J. Pathology 161:2283-2294 (PMID: 12466142).(2002)
• Song, G.Y., Chung, C.S., Chaudry, I.H., Ayala, A. 2001. MAPK p38 antagonism as a novel method for inhibiting lymphoid immune suppression in polymicrobial sepsis. Amer. J. Physiol. 281:C662-C669 (PMID: 11443065).(2001)
• (For full list download CV-pdf)