Bonnie Blomberg, Ph.D.

Professor of Microbiology and Immunology
Room 3146, Rosenstiel Medical Sciences Building
1600 NW 10th Avenue
Telephone: 305-243-6040
Fax: 305-243-4623
Email: bblomber@med.miami.edu

Research Interests:

Aging B Lymphocytes, Tolerance to Transplants, and Immune Response in Breast Cancer Patients.

Our laboratory is funded for three major projects within the immune system: 1) to determine the molecular and cellular basis for the decline in the humoral immune response seen in aged mice; 2) to generate immune tolerance to foreign grafts, specifically kidney transplants; and 3) to assess the effect of psychosocial intervention on the immune system in breast cancer patients.

Regulation of B lymphopoiesis during Aging

Our laboratory, in collaboration with Dr. Richard Riley in this department, has shown decreased pre-B cell numbers and pre B receptors in aged mice when compared with young mice (2-4 months of age), aged mice, those greater or equal to about 80% of their full life span (22-24 months of age), have a poor immune response, one aspect of which is qualitatively poorer antibodies. We have found that the transcription factor, E47, a key regulator of B cells, is decreased in both aged bone marrow precursor B cells and splenic activated B cells (1, and ref. therein). E47 is necessary for Ig class switch, which we have also shown is reduced in aged mice (4, 8). We have begun to determine the molecular regulation of E47 in aged splenic B cells (8,10,11), as well as in aged B cell precursors in the bone marrow (3,5,11,12). Our current studies will reveal the molecular and cellular causes of these defects in the aged humoral immune response and attempt to reverse these defects in genetically altered cells and mice.

Generation of Immune Tolerance to Human Allogeneic Kidney Transplants

As part of an ongoing program with the Department of Surgery, Division of Transplantation, our laboratory is collaborating to devise molecular and cellular avenues to generate tolerance, eventually in humans, for transplanted allogeneic kidneys. To accomplish the generation of tolerance of patients to their kidney grafts will require "retraining" of each patient's immune system to recognize the foreign antigens, notably MHC class I and II as "self". We are embarking on this by using gene therapy to introduce the foreign genes into self antigen presenting cells (APCs) (6). We are also doing experiments to inhibit costimulatory molecules in human APC to induce T regulatory cells with the goal to inhibit alloreactive responses (2,7).

Quality of the Immune System in Breast Cancer Patients in Response to Psychosocial Intervention

Another project in our laboratory is clinical research with breast cancer patients. In collaboration with Drs. Michael Antoni and Charles Carver, in the Department of Psychology, we are measuring the status of various immune parameters in the patients in response to psychosocial intervention (e.g., group therapy, stress reduction). We have shown that intervention patients have an improved immune response as seen by the ability of their T cells to proliferate in response to an antigen-specific receptor stimulus (anti-CD3), NK/LAK cytotoxic function as well as TH1 cytokine production resulting from T cell stimulation (9 and manuscript in preparation). Humoral antibody response changes are also being measured to Muc-1, an antigen present on breast cancer cells. Current/future studies will be directed toward measuring the tumor-specific immune response of these patients. These studies are important to allow optimal immune response in cancer patients which will better detect/destroy residual cancer and allow better patient survival.

Selected Publications:

1. Frasca, D., Nguyen D., Riley R.L., Blomberg B.B. (2003) Decreased E12 and/or E47 transcription factor activity in the bone marrow as well as in the spleen of aged mice. J. Immunol., 170:719-726.
2. Mathew, J.M., Blomberg, B.B., Fuller, L., Burke, G.W., Ciancio, G., Kenyon, N., Ricordi, C., Tzakis, A.G., Esquenazi, V., Miller, J. (2003). A novel micro-cell-mediated lympholytic assay for the evaluation of regulatory cells in human alloreactive CTL responses. J. Immunol. Methods 272:67-80.
3. Frasca, D., Nguyen, D., Van der Put, E., Riley, R.L., Blomberg B.B. (2003) The age-related decrease in E47 DNA-binding does not depend on increased Id inhibitory proeteins in bone-marrow-derived B cell precursors. Front Biosci. 8:110-116.
4. Frasca, D., Nguyen D., Riley R.L., Blomberg B.B. (2003) Effects of aging on proliferation and E47 transcription factor activity induced by different stimuli in murine splenic B cell. Mech. Ageing Dev. 124: 361-369.
5. Van der Put, E., Sherwood, E.M., Blomberg, B.B., Riley, R.L. (2003) Aged mice exhibit distinct B cell precursor phenotypes differing in activation, proliferation and apoptosis. Exp. Gerontol. 38:1137-1147.
6. Blomberg B.B., Hussini S, Fainman H, Mathew JM, Hernandez A, Carreno M, Hnatyszyn HJ, Garcia-Morales R, Fuller L, Rosen A, Ricordi C, Tzakis A, Miller J, Esquenazi V. Retroviral transduction of an allogeneic class II gene into human bone marrow down regulates allo-immune reactivity. Hum Immunol. 2003 Oct;64(10 Suppl):S128.
7. Hernandez A, Lindner I, Blomberg B.B., Hussini S, Burger M, Mathew JM, Carreno M, Garcia-Morales R, Fuller L, Jin Y, Rosen A, Lee KP, Miller J, Esquenazi V. Suppression of allogeneic T cell proliferation through blocking of NF-KB in the differentiation process of human dendritic cells. Hum Immunol. 2003 Oct;64(10 Suppl):S128.
8. Frasca, D., Van der Put, E., Riley, R.L., Blomberg B.B. (2004) Reduced Ig class switch in aged mice correlates with decreased E47 and activation-induced cytidine deaminase. J. Immunol.172:2155-2162.
9. McGregor, B.A., Antoni, M.H, Boyers, A., Alferi, S., Cruess, D., Kilbourn, K.M., Blomberg, B.B., and Carver, C.S. (2004) Cognitive behavioral stress management increases benefit finding and immune function among women with early stage breast cancer. J. Psychosom. Res, 56:1-8.
10. Frasca D., Nguyen D., Riley R.L., Blomberg B.B. (2004) Effects of aging on DNA-binding activity of the E47 transcription factor in splenic B cells. Mech. Ageing Dev. 125:111-112.
11. Frasca, D., Van Der Put, E., Riley, R.L., Blomberg, B.B. (2004) Age-related differences in the E2A-encoded transcription factor E47 in bone marrow-derived B cell precursors and in splenic B cells. Exp. Gerontol., 39:481-489.
12. Van der Put, E., Frasca, D., King, A.M., Blomberg, B.B., Riley, R.L. (2004) Decreased E47 in senescent B cell precursors is stage specific and regulated post translationally by protein turnover. J. Immunol. 173:818-827.