Dr. Mohammed's research focuses on (a) Characterization of an immunocompetent animal model resource for triple-negative breast cancer and investigation of immunopreventative and immunotherapeutic approaches such as vaccines and CAR T therapy; (b) Studying mechanisms of cancer dissemination through the lymphatic system; (c) Studying the biology of triple-negative breast cancer, and (d) Addressing cervical cancer inequality and development of point-of-care-test
- Characterization of an immunocompetent animal model resource for triple-negative breast cancer and investigation of immunopreventative and immunotherapeutic approaches such as vaccines and CAR T therapy.
While many cell lines and animal models are available to research and understand cancer in the Caucasian population in the laboratory, these resources are scarce for people of color. Triple-negative breast cancer is the most aggressive and lethal form of breast cancer. It is predominately diagnosed in women of African ancestry, and they are more likely to die from it despite advancements in treatment and prevention strategies. The lack of studying the development and progression of the disease in the laboratory has hindered a better understanding of the early molecular events involved in triple-negative breast cancer's evolution and invasive nature. It has also limited the prospect of preventing or treating this lethal disease.
Our laboratory put considerable effort into characterizing an immunocompetent animal model that spontaneously develops ductal carcinoma in situ (DCIS) that progresses to invasive cancer in my laboratory. Our work showed that 2/3 of the dogs develop triple-negative mammary tumors naturally without any chemical or genetic manipulation. Furthermore, we have documented the similarities between the animals' and humans' tumors in morphology, hormonal expression, molecular markers, epigenetics, prevalence, and imaging characteristics. The work was funded by the Department of Defense (DOD) Idea Award. Our findings were reported in many journals, including the American Association for Cancer Research (AACR) Journal of Cancer Epidemiology, Biomarkers, and Prevention. The work is featured on the journal's cover page, accompanied by an editorial by Edouard Cadieu and Elaine A. Ostrander of the Cancer Genetics Branch at the National Human Genome Research Institute. Also, the work was published in the Veterinary Pathology, Cancer Prevention, Cancers, and Scientific Reports journals and covered by many news agencies. Recently, with immunotherapy's popularity, NCI and the scientific community consider dogs an excellent model for evaluating cancer therapeutics.
Ongoing studies in my laboratory using our dog model.
- Immunoprevention studies. Women with ductal carcinoma in situ (DCIS) and early-stage cancer are at increased risk of developing invasive breast cancer. Currently, these women can be clinically identified and surgically treated. However, the surgery has adverse long-term health effects, as these women suffer weight gain, fatigue, disfiguring, and depression. Hence, new strategies to prevent cancer development with no long-term adverse effects are urgently needed. In the pursuit of addressing these challenges, we further characterized our immunocompetent animal and studied progression along the cancer continuum. We identified proteins only expressed at the early stages of triple-negative tumors and not at an immunogenic level in healthy tissues in both species. DOD currently funds the project to formulate vaccines using these proteins and test their safety and efficacy in dogs with triple-negative DCIS and early-stage cancer.
- Immunotherapy studies - CAR T therapy for triple-negative breast cancer patients. Although only one out of every six breast cancer cases is triple-negative breast cancer, these tumors account for a disproportionate percentage of breast cancer deaths. Chemotherapy remains the standard of care for triple-negative breast cancer; however, the response of triple-negative breast tumors to chemotherapeutic drugs is often poor. As a result, most patients suffer dire side effects and die of complications caused by their disease burden. Hence, there is a need for more effective treatments for triple-negative breast cancer with limited long-term adverse effects. Our laboratory created canine CAR-T cells and developed a strategy to sensitively manage CRS and tumor heterogeneity while preserving CAR T cell cytotoxicity and proliferation. We prepared a modified CAR T cell that can only engage a cancer cell when a bispecific adaptor is present to bridge the CAR T cell and its malignant target. The adaptor (short-lived, t1/2 ~20 minutes) can target many different tumor-specific proteins/receptors, allowing a small cocktail of adapters to mediate the killing of multiple heterogeneous cancer cells by the same CAR T cell. Our proposed study's overall goal is to use our immunocompetent dog model to understand and find solutions for the limitations of CAR T cell therapy to make them safer and more effective in treating TNBC.
- Studying mechanisms of cancer dissemination through the lymphatic system.
Although breast cancer is more common in women of European ancestry, women with African ancestry are more likely to develop advanced disease that metastasizes to other organs at a young age (<50 years old). Triple-negative breast cancer metastasizes through the systemic and lymphatic systems. Although there is a plethora of research on understanding and preventing systemic metastasis, not much on the lymphatic spread of cancer cells from the primary tumor to the lymph node and then to distant sites. My laboratory is researching how tumor cells gain access to the lymphatic capillaries at genetic and molecular levels.
- Studying the biology of triple-negative breast cancer. In the pursuit of identifying specific targeted therapy for triple-negative breast cancer, our laboratory used proteomic and metabolomic approaches to identify the altered proteins and metabolites of triple-negative breast cancer (ER, PR, HER-2 negative subtype) and luminal A breast cancer (ER and PR positive and HER-2-negative subtype) within (African American women) and across race (in comparison to Caucasian women). The work indicated distinct protein and metabolic profiles and pathways of triple-negative breast cancer and luminal A breast cancer in both groups of women that we are currently investigating further in our laboratory.
- Addressing cervical cancer inequality and development of point-of-care-test. There is an inequity between high-income countries (HICs) and low- and middle-income countries (LMICs) in cervical cancer burden. Cervical cancer is the second most diagnosed cancer and the major cause of mortality among women in LMIC, even though cervical cancer is preventable. Our laboratory is developing a simple paper-based colorimetric test for point-of-care (similar to the pregnancy test) cervical cancer screening with 90% sensitivity and 95% specificity. In addition to being sensitive and specific for invasive cervical cancer and its precursors, no specialized infrastructure or personnel are required to perform the test. It would be affordable for LMIC markets. Screening for early-stage disease in LMICs would enable simple treatment methods via cryotherapy before the disease progresses to advanced stages of cancer.