Research Interests
My research in the Department of Genetics at LSUHSC focuses on translational oncology, specifically in pancreatic ductal adenocarcinoma (PDAC) and breast cancer. Our lab is currently engaged in three major projects:
1. The Role of Protein S in Pancreatic Ductal Adenocarcinoma (PDAC)
In collaboration with Dr. Rinku Majumder (Department of Interdisciplinary Oncology, LSUHSC), we are investigating the role of Protein S (PS), a natural anticoagulant, in PDAC progression.
PDAC is one of the deadliest cancers, with a 5-yearsurvival rate below 10%. Up to 40% of PDAC patients develop venous thromboembolism (VTE), a complication that significantly worsens prognosis. Current anticoagulants, such as direct oral anticoagulants (DOACs), do not adequately address the dual challenges of thromboembolism and tumor progression in PDAC.
Our research has revealed that PDAC patients exhibit significantly reduced plasma PS levels, raising two key questions:
Our preclinical studies demonstrate that PS possesses both antithrombotic and antitumor effects in PDAC models. Additionally, we are collaborating with clinicians to evaluate PS expression as a potential biomarker for PDAC progression.
Selected Publications:
https://www.sciencedirect.com/science/article/pii/S0049384824003657?via%3Dihub
https://www.mdpi.com/1422-0067/25/11/5661
2. Gut Microbiome Modulation to Enhance Immunotherapy in Triple-Negative Breast Cancer (TNBC)
Triple-negative breast cancer (TNBC) accounts for ~15%of all breast cancers and is the most aggressive subtype, disproportionately,disproportionately affecting Black and premenopausal women. There are few targeted therapies for TNBC, with anti-PD-1 immunotherapy being the preferred approach for early-stage disease.
Emerging evidence suggests that modulating the gut microbiome influences immunotherapy efficacy in various cancers, though its role in TNBC remains unclear. Notably, obesity exacerbates TNBC progression and contributes to gut dysbiosis.
Our preliminary data show that probiotic supplementation prior to anti-PD-1 therapy improves overall survival in an obese TNBC mouse model. This finding raises critical questions:
We are investigating the mechanistic role of the microbiome in promoting CD8+ and CD4+ T-cell activity, elevating IFN-γ, and downregulating proinflammatory cytokines that contribute to TNBC progression. Our studies incorporate both mouse models and patient-derived samples to assess whether gut microbiome manipulation can enhance immunotherapy outcomes in TNBC.
Selected Publication:
https://www.mdpi.com/2072-6643/13/10/3656
3. Targeting Notch Signaling to Overcome Endocrine Resistance in HR-Positive Breast Cancer
Despite advances in metastatic hormone receptor (HR)-positive breast cancer treatment, endocrine resistance inevitably develops, limiting long-term therapeutic success. Second-line targeted therapies offer only moderate efficacy, while third-line options are largely ineffective and often toxic.
Notch signaling plays a pivotal role in endocrine resistance in HR-positive breast cancer. Previous Notchinhibitors showed promise but failed due to unacceptable toxicities in clinical trials. We are investigating CB-103, a novel, first-in-class, orally active Notch transcription complex inhibitor. Unlike older Notch-targeting agents, CB-103 has a unique mechanism of action and does not induce the severe gastrointestinal toxicities observed in previous trials.
We hypothesize that:
Our research aims to develop a safer, more effectiveNotch-targeted therapy for overcoming endocrine resistance in HR-positivebreast cancer.
https://www.mdpi.com/2072-6694/15/15/3957
https://www.nature.com/articles/s41573-020-00091-3
Conclusion
Through these projects, our lab is committed to advancing translationaladvancingtranslational cancer research by exploring novel therapeutic approaches for PDAC and breast cancer. Our work integrates molecular insights, preclinical models, and clinical collaboration to improve patient outcomes.
For more details, publications, or collaboration inquiries, please feel free to reach out to Smaju1@lsuhsc.edu
