Microbiology and Immunology

The following grants/studies are under way in the Department of Microbiology and Immunology within the School of Medicine.

Molecular microbial pathogenesis training program
Researcher:
Fernando Villalta, Ph.D.
Funding Source:
National Institute of Allergy and Infectious Diseases (NIAID)
Project Summary: 
  Highly interactive Meharry Medical College and Vanderbilt University mentors who conduct cutting-edge research in molecular microbial pathogenesis participate in this training. The program, for trainees committed to infectious diseases careers, offers trainees opportunities for new discoveries and breakthroughs in the study of the pathogen-host interactions of microbes causing disease including biodefense agents. The innovative features of this program are grounded on cutting-edge science and molecular approaches to study the pathogenesis of microbe-host cell interactions in the following areas: (i) Microbial attachment to receptors, invasion and replication; (ii) Functional genomics and systems biology of microbial infections; (iii) Cell host signaling evoked by pathogens including toxins; (iv) Unique pathogen target genes required for survival; (v) Structural biology and function of new microbial virulent factors; and (vi) Interactions of novel immune molecules with pathogens.


Research training in cardiovascular biology at Meharry
Researcher: Fernando Villalta, Ph.D.
Funding Source: National Heart, Lung and Blood Institute (NHLBI)
Project Summary: This is the third renewal of a NHLBI-supported Minority Institutional Research Training Program in cardiovascular biology at Meharry Medical College (MMC) that will focus in the considerable strengths and diversity of multidepartmental research in cardiovascular biology at MMC and Vanderbilt University School of Medicine (VUMC) into a unique and coherent framework for specialized training. The proposed program will support five pre-doctoral trainees per year and will involve 28 faculty members at MMC and VUMC. Three departments including Cardiovascular Biology at MMC and six departments at VUMC, participate in the program. The research training will focus in cardiovascular biology using cutting edge science and approaches to elucidate mechanisms causing cardiovascular as well as hematologic diseases.


Mechanism based targeted therapies for membranous nephropathy
Researcher
: Dorin Bogdan Borza, Ph.D.
Funding Source: Satellite HealthCare, Inc.
Project Summary: Membranous nephropathy (MN) is a major cause of nephrotic syndrome in adults. Up to 40 percent of patients progress to end-stage kidney disease, and another 30 percent suffer from complications of persistent proteinuria and chronic kidney disease. Current therapies are unsatisfactory. Development of much-needed novel therapies require a better understanding of the pathogenic mechanisms. This study will test the hypothesis that the formation of subepithelial immune complexes promoting complement activation via the alternative pathway plays a central role in the pathogenesis of membranous nephropathy, mediating damage to the glomerular filtration barrier and proteinuria. It aims to determine whether targeted therapies specifically inhibiting the activation of the terminal complement cascade or of the alternative pathway , as well as the ablation of plasma cells producing pathogenic antibodies, are effective strategies for ameliorating glomerular damage and proteinuria in animal models of MN. The new knowledge gained from these studies may eventually translate into new treatments for human disease.

 


Mechanism of biogenesis of atypical alphaviruses
Researcher: Raju Ramasamy, Ph.D.
Funding Source: National Institute of Allergy/Infectious Diseases (NIAID)
Project Summary: Dr. Raju's long-term goal is to elucidate the pathways of alphavirus RNA genome repair and remodeling leading to the generation of atypical viruses in infected host cells. Alphaviruses are an important cause of emerging viral encephalitides in animals and humans and are significant biodefense agents. Delineating these pathways should lead to strategies to control emergence of outbreaks of alphaviruses and perhaps other mosquito-transmitted RNA viruses. Since alphaviruses are vigorously pursued as gene therapeutic and vaccine delivery vehicles, the team's work will also be useful in the development of improved RNA vectors.



Research Centers in Minority Institutions (RCMI)- Molecular Biology Core Component
Researcher
: Robert Holt, Ph.D.
Funding Source: National Institute on Minority Health and Health Disparities (NIMHD)
Project Summary: Dr. Holt is the Scientific Director of the Molecular Biology Core at Meharry Medical College supported by RCMI. This core is a multi-functional facility that provides to faculty, students and staff of the college the primary service of DNA sequencing but also provides access to shared equipment housed in a centralized location and facilitates convenient and rapid access to frequently used molecular biological reagents. This core supports the enhancement of the research enterprise at the College.



Mitochondrial inner membrane protein translocase in trypanosoma brucei
Researcher:
Minu Chaudhuri, Ph.D.
Funding Source: National Institute of General Medical Sciences (NIGMS)
Project Summary: African trypanosomiasis, a fatal disease in humans as well as in domestic animals, is caused by the parasitic protozoa, Trypanosoma brucei. As available drugs for this disease are inadequate, it is critical to identify targets to design new drugs. Import of essential mitochondrial proteins is crucial for survival of this parasite in mammalian hosts. Therefore the unique structure and function of mitochondrial protein import molecules could be exploited as novel drug target(s).



Enhancement of the efficacy of conventional anticancer compounds through the repression of SNAI proteins in aggressive breast cancer cells Researcher: Gautam Chaudhuri, Ph.D.   
Funding Source: Department of Defense (DOD)
Project Summary: Dr. Chaudhuri's team is studying the role of the SNAI family of transcriptional repressors in vitamin D metabolism as well as in vitamin D and anti-estrogen resistance development in breast cancer with emphasis on breast cancer in African-American breast cancer patients. Because inhibition of VDR expression and elevation of cyclin D1 are clinically associated with vitamin D3 and anti-estrogen resistance development in breast cancer patients, rational strategies to reduce the expression of SNAI proteins will enhance the therapeutic efficacy of these drugs against breast cancer. Therefore, the knowledge and the reagents to be generated from the proposed research will have a direct impact on improving the effectiveness of anti-estrogen and vitamin D therapy for patients with SNAI-high and VDR-low breast cancers.


 

Novel trypanosome receptor for thrombospondin-1
Researcher
: Pius N. Nde, Ph.D.
Funding Source: National Institute of Allergy and Infectious Diseases (NIAID)
Project Summary:  Trypanosoma cruzi, the causative agent of Chagas heart disease up-regulates the expression of host thrombospondin-1 (TSP-1), early during the process of infection. TSP-1 binds specifically to the surface of invasive forms of T. cruzi trypomastigotes and knocksdown of host TSP-1 by RNA interference cause significant inhibition of T. cruzi infection. Our working hypothesis is that T. cruzi trypomastigotes up-regulate host TSP-1 that interacts with trypanosome surface receptor(s) to enhance the infection of heart cells. We are interested in identifying and characterizing the novel T. cruzi TSP-1 binding molecule on the surface of the parasite and determining the in vivo role of TSP-1 gene in the process of T. cruzi infection using aTSP-1 KO mice model. Our research will facilitate the development of specific molecular intervention strategies to prevent Chagas heart disease.