Troy D. Randall, Ph.D.

Troy D. Randall, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 695
Rochester, NY 14642

Office: (585) 276-4613
Lab: (585) 273-3279
Administrative: (585) 273-3213
Fax: (585) 442-3214

Research Bio

Pulmonary Immunity to Viruses, Tumors and Allergens: One project in my lab is to determine how local lymphoid tissues, such as inducible Bronchus Associated Lymphoid Tissue (iBALT), develop and function. We find that, although naïve mice lack lymphoid tissues in their lungs, iBALT forms in response to infection or inflammation. Importantly, immune responses to influenza are generated in iBALT and mice with iBALT are more resistant to influenza than normal mice. Thus, iBALT is not simply an area of inflammation, but is a site that actively regulates respiratory immunity in a way that leads to less morbidity and mortality. Consistent with this idea, new data suggest that humans with lung cancer who also develop iBALT have a better prognosis than those who not. Thus, we are currently exploring ways to induce iBALT in mouse models of lung cancer to determine whether the induction of iBALT will lead to cancer regression. In contrast, we also find that iBALT is generated in the lungs of humans with a wide variety of pulmonary pathologies. In particular, humans with rheumatoid lung disease often develop iBALT. We suspect that in this case, iBALT is responding to autoantigen and exacerbating lung disease. Interestingly, we have also found that there is a developmental window in neonates during which iBALT is most easily formed. This window corresponds to a time when children are at risk of developing asthma in response to respiratory viruses, such as RSV. Thus, iBALT is probably involved in both helpful and harmful immune responses in the lung.



Peritoneal Immunity to Tumors and Commensal Organisms: We are also studying the development and function of lymphoid tissues in the peritoneal cavity, including milky spots of the omentum and the Fat-Associated Lymphoid Clusters (FALC) in the mesentery. These tissues are embedded in abdominal fat and collect fluids, particulates and metastasizing tumor cells from the peritoneal cavity. Although we find that milky spots are functional secondary lymphoid organs, we also find that they suppress immune response to peritoneal tumors. Given that peritoneal tumors, such as ovarian carcinomas, shed cells that metastasize to the omentum, it is essential that we understand the mechanisms that promote tumor growth in the omentum in order to treat peritoneal tumor metastases. We suspect that the normal function of the omentum is to maintain tolerance to commensal organisms and food antigens. Thus, the omentum has evolved to generate Tregs and Th3 cells that produce IL-10 and TGF? and help B cells switch to IgA. However, in the context of tumor antigens, these same functions impair anti-tumor immunity. Thus, my lab is determining the mechanisms by which the omentum suppresses immune responses to peritoneal tumors and maintains tolerance to commensal and food antigens.

Control of CD8 T cell Responses to Viruses and Tumors: We also study how CD40 signaling controls CD8 T cell responses. We find that CD40 signaling is key for CD8 responses to influenza and tumor antigens, but that CD4 T cells are dispensable. This scenario is difficult to reconcile with the paradigm that CD40L is expressed by CD4 T cells. Nevertheless, we now believe that CD4 effector T cells provide CD40L in order to counteract the activities of CD4 Tregs. Thus, in the absence of all CD4 T cells, CD40L is not required. Our data suggest that there is a competition between CD4 effectors and Tregs to control the activity of APCs that regulate the priming, expansion and differentiation of CD8 T cells. We have identified the important dendritic cell populations that are required for CD8 T cell responses to influenza and are now determining how CD4 effectors and Tregs control the activity of these cells. Interestingly, different class I restricted epitopes have different requirements for CD4 cells and CD40 signaling, suggesting that each epitope is processed and presented by different cells, which are activated by different mechanisms.

Recent Journal Articles

Showing the 5 most recent journal articles. 81 available »

2011 May
Lamere MW, Moquin A, Lee FE, Misra RS, Blair PJ, Haynes L, Randall TD, Lund FE, Kaminski DA. "Regulation of antinucleoprotein IgG by systemic vaccination and its effect on influenza virus clearance." Journal of virology.. 2011 May; 85(10):5027-35. Epub 2011 Mar 02.
2011 Apr 1
Lamere MW, Lam HT, Moquin A, Haynes L, Lund FE, Randall TD, Kaminski DA. "Contributions of antinucleoprotein IgG to heterosubtypic immunity against influenza virus." The Journal of immunology : official journal of the American Association of Immunologists.. 2011 Apr 1; 186(7):4331-9. Epub 2011 Feb 25.
2010 Oct
Kaminski DA, Randall TD. "Adaptive immunity and adipose tissue biology." Trends in immunology. 2010 Oct; 31(10):384-90.
2010 Aug 2
Cruz A, Fraga AG, Fountain JJ, Rangel-Moreno J, Torrado E, Saraiva M, Pereira DR, Randall TD, Pedrosa J, Cooper AM, Castro AG. "Pathological role of interleukin 17 in mice subjected to repeated BCG vaccination after infection with Mycobacterium tuberculosis." The Journal of experimental medicine.. 2010 Aug 2; 207(8):1609-16. Epub 2010 Jul 12.
2010 Aug 2
Misra RS, Shi G, Moreno-Garcia ME, Thankappan A, Tighe M, Mousseau B, Kusser K, Becker-Herman S, Hudkins KL, Dunn R, Kehry MR, Migone TS, Marshak-Rothstein A, Simon M, Randall TD, Alpers CE, Liggitt D, Rawlings DJ, Lund FE. "G alpha q-containing G proteins regulate B cell selection and survival and are required to prevent B cell-dependent autoimmunity." The Journal of experimental medicine.. 2010 Aug 2; 207(8):1775-89. Epub 2010 Jul 12.

Education

PhD | Microbiology and Immunology | Duke University1992
BS | Chemistry | University of Denver1987

Post-Doctoral Training & Residency

Postdoctoral Fellow with Dr. Ronald Corley Duke University 1992
Postdoctoral Fellow with Dr. Irving Weissman Stanford University 1996
Predoctoral Fellow with Dr. Ronald Corley Duke University 1992