Areas of Research
- Breast Cancer
- DNA Damage Response
- DNA Repair
- Gene Expression
- Molecular Biology
- Targeted Therapy
- Tumor Suppression
- Uterine Cancer
The KeyHunt Laboratory is directed by Dr. Khandan Keyomarsi and Dr. Kelly K. Hunt. The lab is focused on clinical and translational cancer research in solid tumors, primarily in breast cancers and sarcomas.
Our laboratory has developed a research program for identifying novel therapeutic strategies and prognostic markers based on alterations in G1/S and G2/M checkpoints in tumor cells focusing on solid tumors such as breast, sarcoma, pancreatic and lung cancers. We are currently involved in five primary areas of research, which fall into translational and basic research categories:
1) Inhibition of LMW forms of cyclin E as a therapeutic target
in combination therapy for triple negative breast cancer.
2) Delineation of how the alteration of cyclin E, a G1 cyclin,
could lead to the tumorigenic phenotype and determination of the oncogenic potential of the altered forms of cyclin E in breast cancer.
3) Determination of the mechanism of action of intracellular
elastase and its inhibitor elafin in tumorigenesis and subsequent metastasis.
4) Examination of mechanisms of action and resistance to CDK4/6 inhibitors in ER positive breast cancer patients.
5) Identification of novel treatment strategies, targeting the
cell cycle, for soft-tissue sarcomas.
The translation of these research directions into clinical trials is the main focus of our laboratory.
Low molecular weight cyclin E isoforms (LMW-E) are generated by neutrophil elastase-mediated proteolytic cleavage, removing the N-terminal nuclear localization signal. LMW-E isoforms accumulate in the cytoplasm where they inappropriately interact with cytoplasmic proteins such as ACLY. The altered biochemistry of LMW-E results in hyperactivation of CDK2, resistance to endogenous CDK-inhibitors (p21CIP1 and p27KIP1), and altered substrate interactions, which results in enhanced cell cycle progression, genomic instability, and other pro-tumorigenic features. Evaluation of LMW-E by western blot (protein size) or immunohistochemistry (cytoplasmic localization) is prognostic of poor prognosis and predicts failure of standard treatment modalities.
Keyomarsi & Hunt Training Grants
CPRIT Research Training Grant
CPRIT Research Training Program provides fundamental, interdisciplinary, and innovative training in cancer research at MD Anderson. This program is the continuation of highly successful and comprehensive training programs supported by the Cancer Prevention Research Institute of Texas (RP101502, RP140106, and RP170067). Our program includes three tracks: the CPRIT TRIUMPH (Translational Research in Multidisciplinary Programs) post-doctoral, CPRIT Graduate Scholar, and CPRIT Summer Undergraduate Research Programs.
Meet the Team
KeyHunt Lab (front row, left to right): Marc Pina, Dr. Amriti Lulla, Dr. Khandan Keyomarsi (PI), Dr. Kelly K. Hunt (PI), Dr. Kari Brewer Savannah, Dr. Komal Rasputra; (middle row, left to right): Dr. Sophia Mastoraki, Dr. Yanlai Lai, Dr. Juliana Navarro, Dr. Min Yi, Dr. Xian Chen, Dr. Yan (Esther) Wang, Dr. Xiayu Rao (Collaborator), Dr. Bisrat Debeb (Collaborator); (back row, left to right): Dr. Kwang Hui Low, Ashley Hamlin, Mi Li, Tuyen Bui, Dr. Nicole Kettner, Nghi Lam, Dr. Cansu Karakas.