Research Information
Research Interests
Expertise areas: B cell responses to transplantation and in host defense; Genomic determinants of immunity; Immunoglobulin gene diversification; Immunotherapies.
Dr. Cascalho’s current research resides in fields of transplantation immunology, host-defense, immunotherapies, genetics and vaccine design.
Her interest on B cell biology was sparked by her early work on molecular mechanisms of immunoglobulin gene recombination and mutation and led to the discovery that DNA mismatch repair drives B cell Ig gene hypermutation.
Dr. Cascalho and her colleagues established that B cell and immunoglobulin diversity promote T cell development and the establishment of a diverse antigen receptor (TCR) repertoire. They also discovered that the TNRSF13B gene encoding a receptor (also abbreviated as TACI) expressed mostly by B cells is an immune-regulatory gene. These findings suggested that TNFRSF13B gene diversity protects populations against unknown pathogens by assuring a wide array of immune responses that while disadvantageous in some individuals and in certain conditions, e.g. transplantation, will protect most against dissemination of microbes that evolved to explore the vulnerabilities of host defense.
The research has eventuated in a number of disclosures and patents, papers in leading scientific journals (Nature, Science, Nature Medicine, Immunity, J Exp Med, J Clin Invest and others), the prestigious Science Award for young investigators and in grant awards from the NIH, DoD, Gates Foundation, State of Michigan and from the US-Israel Bi-National Science Foundation.
Research Projects
AI 173950-NIH/NIAID: TNFRSF13B polymorphisms and immunity to transplantation (PI)
Major Goals: 1: To identify genomic polymorphisms of the TNFRSF13B gene that condition B cell responses and the propensity for rejection in kidney transplant recipients. 2: To trace the evolution of donor-specific B cell clones in subjects with and without TNFRSF13B polymorphisms and 3: To determine how select TNFRSF13B variants condition B cell responses
AI 151588-NIH/NIAID: Donor-Specific B Cells in Transplantation (PI)
The major goal of this project is to determine the properties of donor-specific B cells in recipients that maintain stable graft function and in those that undergo rejection.
AI117561-NIH/NIAID: TNRSF13B polymorphisms and the control of innate B cell responses – a double edged sword (PI)
Goals for this project are 1: To determine how tnfrsf13b controls infection and dissemination of C. rodentium 2: To determine how IgA induces virulence.
CASE-283529 UM-MTRAC for Life Sciences: C3d Immunotherapies to treat Multiple Myeloma and related conditions.
The research goals are to evaluate the efficacy of a novel immunotherapy, a C3d peptide, to treat MM and to delete pre-malignant B expanded B cell clones.
GM 140359 01: A novel rabbit model for easy monoclonal antibody production (PI)
We propose to gene edit the rabbit TACI gene with the goal to enhance the hybridoma efficiency in rabbits.
AI 154128 01: The role of Absent in Melanoma 2 (Aim2) in CD8+ T cell regulation and Helicobacter-induced gastric pathology (Co-I)
To understand the role of AIM2 inflammasome in regulating H. pylori gastritis.
AI123262 Accommodation in Transplantation, completed in 2019 (PI)
The research addressed two overarching questions: how often and when after transplantation do B cell responses specific for the transplant donor occur and are the B cell responses leading to accommodation different from the B cell responses leading to rejection.
W81XWH-18-1-0721: Mutable Vaccines for Emerging Infectious Threat, completed in 2020 (PI)
The research will determine how fast the vaccine mutates and how diverse are its products. The research will also determine how much immunity the mutant products generate and whether that immunity mimics the types of immunity thought potentially to control of HIV