Rao Lab

Manjeet Rao, PhD

Rao Lab Members

Director (Interim) – Greehey CCRI

Co-Leader, Experimental, and Development Therapeutics,
Mays Cancer Center; Discipline Director, Cancer Biology – Graduate Program.

Rank: Professor
Department: Cell Systems & Anatomy
Office: 4.100.10
Tel: 210-562-9119
Email:

The overall goal of my laboratory is to develop more potent and less toxic drugs for treating adult and pediatric cancer patients. We have employed unbiased high throughput genomewide functional screens as well as small molecular screens to identify novel targets that are critical for growth, progression, and drug sensitivity in medulloblastoma and osteosarcoma. In particular, using the loss of function screens, we have identified key genes that play critical/causal roles in the growth and metastasis as well as in the chemo-sensitivity of osteosarcoma. Furthermore, by performing small molecule library screens, we have identified inhibitors of these proteins that may act as novel therapeutics for treating osteosarcoma. Another area of our interest involves understanding the role of RNA epigenetic modifiers in osteosarcoma. In particular, we have identified RNA demethylase as a driver protein that may amplify oncogenic programs in osteosarcoma by regulating DNA replication, DNA repair, and genomic integrity. We aim to develop novel small molecule inhibitors against RNA demethylase that can potentially serve as RNA mimetics, which can abolish the activity of this protein in OS.

Our approach includes a combination of fluorescence polarization-based high-throughput screening using small molecule libraries, cell-based studies, and structure-guided development of novel inhibitors. Towards that goal, we have identified a unique RNA target sequence comprising the core m6 A motif (GGACU) that binds to RNA demethylase with high affinity. Using this unique RNA target sequence, we have performed high-throughput screening of the FDA-approved drug library and identified inhibitors that can potentially inhibit the activity of this driver protein. We are currently testing the efficacy of the inhibitor/s in the PDX model. We plan to explore the possibility of repurposing these drugs in clinical trials in near future.

Our research endeavors have resulted in the clinical development of an anti-depression for treating triple-negative breast cancer patients (Imipramine Before Surgery in Treating Patients with Estrogen Receptor-Positive or Triple Negative Breast Cancer).  This study is a perfect example of a bench-to-bedside initiative.

We have identified novel microRNAs that act as a potent tumor suppressors in medulloblastoma. Interestingly, one of these miRNAs sensitizes vincristine as well as radiation response in c-myc amplified medulloblastoma by targeting microtubule dynamics and DNA damage response. We are currently testing the viability of this miRNA in a non-human primate model (in collaboration with Dr. Brigitte Widermann at NCI). We are in the process of scheduling a pre-IND meeting with the FDA to know more about the required IND-enabling studies.

In addition, we are testing the efficacy of this miRNA in the rat leptomeningioma model. The goal is to test whether the miRNA can be delivered via intraventricular injection to avoid any potential immune response or need for a sophisticated delivery vehicle. In the next 3-years, we plan on taking this miRNA to a phase I clinical trial.

UT Health San Antonio Faculty Profile: Manjeet Rao, PhD

Lab Research

Cancer

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.

microRNA

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 critical for the activity of those proteins.

RNA epigenetics

RNA epigenetics

We were the first group to design novel algorithms that can identify transcriptome-wide methylation and 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 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 miRNA and development. We were the first group to develop an in vivoRNA interference (RNAi) approach 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 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

Lab Staff

Desiree Denman
Teaching Assistant

Daisy Medina
Graduate Research Assistant

Saif Nirzhor
Graduate Student

Subapriya Rajamanickam, PhD
Instructor/Research

Panneerdoss Subbarayalu, PhD
Instructor/Research

Santosh Timilsina, PhD
Graduate Research Assistant

Pooja Yadav, PhD
Postdoctoral Fellow

2021Donald G McEwen, Memorial Summer Undergraduate Research Program Student
  • Shresth Arya
  • Neil Gupta
  • Arhan Rao
  • Lanka Srilalitha (mentor, Dr. Subbarayalu)
Dr. Rao is actively recruiting graduate students to join his lab.

Email all inquiries

 

 

Lab Alumni

Dr. Nourhan Abdelfattah, PhD
Postdoctoral Fellow
Houston Methodist Research Institute

Dr. J.Saadi Imam, PhD, MD
Postdoctoral Fellow – Residency (MD)
Mayo Clinic Jacksonville

Dr. Sanjay Bansal, PhD
Postdoctoral Fellow
Bristol-Myers Squibb

Dr. Behyar Zoghi, MD, PhD
Postdoctoral Fellow – Hematologist
Methodist Hospital, San Antonio

Dr. Yao-Fu-Chang, PhD
Postdoctoral Fellow
Scientific Writer, Dallas

Jason Plyler
Graduate Student
Mirna Therapeutics

Featured News

Science Advances: Predicting and characterizing a cancer dependency map of tumors with deep learning (Aune, Chen, Rao, Houghton & Zheng Labs)

Manjeet Rao, PhD, Awarded NCI, R01 Grant to Test Efficacy of Novel Drug

All news

Rao Lab “In the News.”

Texas Senate Resolution 368: Commending Manjeet Rao for receiving the Presidential Distinguished Junior Research Scholar Award from The University of Texas Health Science Center at San Antonio.

Current Courses Taught By Dr. Rao: