Khalid Sossey-Alaoui, PhD

Associate Professor

Faculty Research Staff at MetroHealth Medical Center

Associate Professor in the Department of Medicine at CWRU

Member of Case Comprehensive Cancer Center

Contact

Address: MetroHealth Medical Center
Rammelkamp Center for Research, R357
2500 MetroHealth Drive, Cleveland, OH 44109

216-778-5275 | [email protected] | [email protected] | Website: Case Comprehensive Cancer Center Profile

Research

Dr. Sossey-Alaoui research interests are in the area of studies of breast cancer, with special emphasis on Triple Negative Breast Cancer (TNBC) subtype. For the past 20 years I have been investigating the signaling pathways that promote the invasion-metastasis cascade of TNBC tumors. My laboratory investigates the molecular mechanisms that regulate the epithelial-mesenchymal transition (EMT) program as well as the those that mediate the cancer stem cell phenotype and chemoresistance in TNBC. Our major research active projects include:

Role of WAVE3 in TNBC progression and metastasis: We established WAVE3, an actin cytoskeleton remodeling and scaffolding protein, as a novel promoter of TNBC development and metastatic progression, doing so by stimulating their acquisition of EMT, invasive, and metastatic phenotypes. Our recent investigations identified a role of WAVE3 in stabilizing β-catenin and, therefore, activating the downstream oncogenic pathways.
Role of YB1 in the invasion-metastasis cascade of TNBC, chemoresistance and cancer health disparities: YB1 is a multifunctional protein that regulates mRNA stability in the cytoplasm, and, in the nucleus, acts as a cancer stem cell (CSC) transcription factor. Targeted-inhibition of YB1 sensitizes TNBC cells to chemotherapy-and radiation-induced cell death, and inhibits progression and metastasis of TNBC tumors by targeting the CSC phenotype. We also identified a potential role of YB1 in the regulation of cell cycle, involving CDK2 and CDK4. More recently, we identified YB1 as being disparately activated in African American (AA) women with TNBC, compared to their Caucasian American (CA) counterparts. Increased YB1 activity correlates with increased resistance to chemotherapy and with worse disease outcomes in AA TNBC. We are currently investigating signaling pathways that involved the YB1-mediated regulation of immune-evasion in TNBC.
Kindlin-2 as a major regulator of the oncogenic signaling of TGF-β and cancer cell senescence: We also established Kindlin-2 as a major player in the modulation of the tumor microenvironment by regulating the CSF-1:EGF:TGF-β signaling axis and a key regulator of EMT during the invasion-metastasis cascade of TNBCs. Kindlin-2 acts as a physical bridge that links TGFbR1 and Integrins to activate the non-canonical TGF-β oncogenic signaling. In the nucleus, Kindlin-2 associate with p53 to regulate cancer cell senescence through the activation of SepinB2/p21/AURK-A signaling axis.
Role of WAVE2 breast cancer progression and metastasis. The interplay between WAVE2 and miR-29 regulates the integrin-mediated modulation of the extracellular matrix and the downstream STAT3 oncogenic signaling in breast cancer.

Funding

Role: Principal Investigator
Source: NCI
Grant: 1R01 CA272621A1.
Title: Role of YB1 in health disparities in triple negative breast cancer.
Amount: $2,824,740
Dates: 04/01/2023 to 03/31/2028
The major goal of this project is to determine the Role of YB1 Phosphorylation (S102) and Nuclear Localization in Tumorigenicity and Chemoresistance in AA TNBC tumors.

Role: Principal Investigator
Source: METAvivor Translational Research Award
Grant: 000986
Title: Role of YB1 in Triple Negative Breast Cancer Metastasis
Amount: $248,751
Dates: 02/01/2023 to 01/31/2025
The major goal of this project is to determine the role of YB1 in TNBC tumorigenicity and chemoresistance.

Role: Principal Investigator
Source: NIH/NCI
Grant: 1 R01 CA 226921
Title: Role of WAVE3 in the development and progression of breast cancer
Amount: $1,830,000
Dates: 12/01/2018 to 04/30/2024
The major goal of this project is to continue my investigations of establishing WAVE3 as a driver of tumor progression and metastasis in triple negative breast cancer and to device novel nanoparticle-based therapeutic options for thus deadly cancer.

Role: Principal Investigator.
Source: NIH/NCI.
Grant: 1R0 CA 226921 S1
Title: Triple Negative Breast Cancer in African American Women.
Amount: $483,000
Dates: 09/01/2020 to 04/30/2024.
In this project, I teamed up with investigators with different expertise in areas of health disparities, bioinformatics, breast cancer pathology to investigate the biological, environmental, and socioeconomic factors that may contribute to the health disparities in African American women with triple negative breast cancer.

Publications

National Library of Medicine – Articles