Dr. Cacalho earned an MD and a PhD training in basic sciences (genetics, molecular biology and immunology). Her current research resides in fields of transplantation immunology, host-defense, immunotherapies, genetics and vaccine design. 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 (currently, 5 R01 and 2 R21), DoD, Gates Foundation, State of Michigan and from the US-Israel Bi-National Science Foundation.

Dr. Cascalho and her team made several seminal discoveries.
(1) Dr. Cascalho's interest on B cell biology was sparked by my 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. This discovery inspired the approach to a mutable-antigen mouse platform to anticipate immune-driven evolution of antigens from mutable viruses.
(2) The team established that B cell and immunoglobulin diversity promote T cell development and the establishment of a diverse antigen receptor (TCR) repertoire. This observation led to current research directed at understanding how functions of B cells impact cellular immunity and regulation of immune responses in human health and disease.
(3) They discovered that the TNRSF13B gene encoding a receptor (also abbreviated as TACI) expressed mostly by B cells is an immune-regulatory gene. TNRSF13B is among the most diverse gene in humans and vertebrates, TNRSF13B defines the type and intensity of innate and adaptive B cell responses, the interactions between B and T cells and in doing so also controls complement activation. Thus, while TNFRSF13B low-functioning alleles are beneficial in host defense blocking microbial transmission and epidemic spread, these same polymorphisms increase inflammation in part owing to decreasing control of complement activation. 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.
(4) They found that the fragment d of the third component of complement (C3d) markedly boosts and accelerates cellular immunity slowing and sometimes reverting progression of tumors. C3d does so by vitiating tumor induced immunosuppression, i.e. the processes that impair immune responses to tumors.