Manjeet Rao, Ph.D.
Deputy Director (interim) Greehey CCRI, Co-Leader, Experimental, and Development Therapeutics, Mays Cancer Center; Discipline Director, Cancer Biology – Graduate Program.
Department: Cell Systems & Anatomy
Research in my laboratory is directed towards developing new, more efficacious, and less toxic treatments for adult and childhood cancers.
The overall goal of Rao laboratory is to develop more potent and less toxic drugs for treating pediatric and adult cancer patients. The Rao research group employs unbiased high throughput genomewide functional screens as well as small molecular screens to identify novel targets that may play a critical role in pediatric and adult cancer growth, progression, and drug sensitivity. We are particularly interested in utilizing microRNAs and small molecule inhibitors as novel therapeutic adjuvants to improve the efficacy of chemotherapy drugs for treating high-risk pediatric brain tumors and triple-negative breast cancers. Another area of our interest involves understanding the role of epigenetic modifiers in cancer development and progression. In addition to cancer, we are interested in understanding the role of microRNA and epigenetic modifiers during development.
We are actively engaged in translational research to discover new, more effective, and safe regimens for treating cancers. Towards that goal, we recently discovered that an anti-depressant and its derivative could block cancer cell’s ability to repair DNA. Our study became the basis for the clinical trial, which is currently underway.
Another focus of my laboratory is to use microRNAs as novel biomarkers and therapeutics for the diagnosis/prognosis and treatment of pediatric brain tumors and adult cancers. Our recent research achievements of safe and efficacious delivery of microRNA using lipid and FDA-approved nanoparticle-based systemic delivery approaches to treat cancers in the mouse tumor model paves the way for a clinical trial in the near future.
In addition to miRNA, using unbiased genome-wide synthetic lethal screens, we have identified novel proteins that play a causal role in tumorigenesis and render cancer cells resistant to cancer treatment drugs. With our expertise in medicinal chemistry, structural biology, silicomodeling, and small molecule screening, we have rationally designed and synthesized several lead small molecules that can interfere with the key residues that are critical for the activity of those proteins.
We were the first group to design novel algorithms that can identify transcriptome-wide methylation as well as differential RNA methylation in normal and disease conditions. Recently, in a groundbreaking study, we showed that writers, erasers, and readers of RNA methylation cross-talk with each other to maintain a level of RNA methylation that is critical for the stability of crucial progrowth/proliferation-specific genes. And, any pro-tumorigenic stimulus that perturbs that cross-talk leads to the uncontrolled activity of those genes, resulting in tumor growth and progression. We are currently investigating the role of specific RNA epigenetic modifiers in children’s and adult cancers.
microRNA and Development
In addition to cancer, my group has made some seminal discoveries in the field of miRNA and development. We were the first group to develop an in vivoRNA interference (RNAi) approach that that mimics the principle by which “microRNAs” are processed (Rao et al., Genes & Dev, 2006). Furthermore, we were first to show that miRNA plays a critical role in chromatin condensation during germ cell development (Chang et al., PNAS, 2012). Recently, in groundbreaking work, we showed that LC3-associated phagocytosis is not only confined to macrophages, but it is actively used by Sertoli cells to engulf and clear germ cells during germ cell differentiation (Panneerdoss et al., Nature Communications, 2018).
Field of study: Adult and Children’s Cancer; MicroRNA; Small Molecule Inhibitors
Subfield of study: Drug development, Translational Research
Research Areas: Cancer, Epigenetics, Development
Relevant Diseases: Medulloblastoma; Osteosarcoma; Breast Cancer; Glioblastoma
Research Techniques: Mouse tumor models; Ex-vivo explants from cancer patients; Nanoparticle-based drug delivery; RNA-seq; Me-RIP-Seq; PAR-CLIP; Fiber analysis; IHC; Routine Molecular biology techniques
Subapriya Rajamanickam, Ph.D.
Panneerdoss Subbarayalu, Ph.D.
Santosh Timilsina, Ph.D.
Graduate Research Assistant
Graduate Research Assistant
Student Research Associate
Dr. Rao is actively recruiting graduate students to join his lab.
Dr. Nourhan Abdelfattah, Ph.D.
Houston Methodist Research Institute
Dr. J.Saadi Imam, Ph.D., M.D.
Postdoctoral Fellow – Residency (M.D.)
Mayo Clinic Jacksonville
Dr. Sanjay Bansal, Ph.D.
Dr. Behyar Zoghi, M.D., Ph.D.
Postdoctoral Fellow – Hematologist
Methodist Hospital, San Antonio
Dr. Yao-Fu-Chang, Ph.D.
Scientific Writer, Dallas