Manjeet Rao, PhD
Deputy Director – Greehey CCRI
Co-Leader, Experimental and Development Therapeutics,
Mays Cancer Center; Discipline Director, Cancer Biology – Graduate Program.
Rank: Professor
Department: Cell Systems & Anatomy
Office: 2.100.10
Tel: 210-562-9119
raom@uthscsa.edu
Our Research
Our laboratory is dedicated to understanding how cancers—particularly pediatric and other aggressive solid tumors—interact with their surrounding environment to drive growth, spread, and resistance to therapy. We focus on the complex cross-talk between tumor cells and the supportive cells, immune system, and extracellular structures that make up the tumor microenvironment. These interactions fuel tumor progression by reshaping metabolism, reprogramming normal cells into tumor-supporting states, remodeling the extracellular matrix, and blocking effective immune responses.
A central goal of our work is to uncover the molecular and cellular mechanisms that allow cancers to adapt under stress, evade immune surveillance, and metastasize. Using state-of-the-art models, imaging, and molecular profiling, we identify critical vulnerabilities in these processes that can be targeted for therapy. Our team develops and tests innovative treatment strategies—including small-molecule inhibitors, antibody-based therapeutics, engineered immune cells, and rational drug combinations—that are designed to disrupt tumor-supportive pathways while reducing toxicity.
By integrating cancer biology, immunology, structural biology, and translational research, our mission is to transform mechanistic insights into next-generation therapies. Importantly, our efforts have already led to successful clinical trials, and patients with cancer are directly benefiting from these advances. Ultimately, we strive to improve survival and quality of life for children and adults facing the most challenging cancers.
Project 1: Understanding Tumor Microenvironment–Driven Metabolic Vulnerabilities in Brain Cancer
Our lab investigates how the tumor microenvironment shapes the growth, progression, and treatment resistance of pediatric brain cancers, with a primary focus on medulloblastoma, the most common malignant brain tumor in children. Despite treatment advances, high-risk medulloblastoma remains challenging due to its tendency to recur, spread within the central nervous system, and resist conventional therapies such as radiation.
We investigate how complex interactions within the tumor microenvironment, including signals exchanged between cancer cells and surrounding supportive cells, drive cancer cell survival, stem-like properties, and treatment resistance. Our research focuses on identifying the secretory factors and key oncogenic signaling pathways that enable tumor cells to reprogram their metabolism, adapt to stress, and maintain their aggressive behavior. A major goal of our work is to uncover how these metabolic adaptations not only support rapid tumor growth but also help cancer cells evade the immune system and spread along the surfaces of the brain and spinal cord. By understanding these interconnected mechanisms, we aim to identify vulnerabilities that can be targeted therapeutically. Our translational research explores novel treatment strategies designed to disrupt these pathogenic interactions and metabolic programs. We test small-molecule inhibitors and other therapies that can be combined with existing modalities like radiation or immunotherapy to improve outcomes and reduce side effects for children with this devastating disease. Ultimately, our goal is to generate the foundational knowledge needed to guide the development of more effective and less toxic treatments for pediatric brain cancer.
Project 2: Epigenetic and Epitranscriptomic Control of Tumor Immunity: Implications for Pediatric and Adult Cancer Therapy
Our lab is dedicated to understanding how epigenetic and epitranscriptomic modifications in pediatric and adult cancers shape the tumor immune microenvironment. We study how these molecular changes enable tumors to evade immune detection by suppressing antigen presentation and limiting the recruitment and activation of immune cells. A central focus of our research is uncovering how these regulatory mechanisms impair both innate and adaptive anti-tumor immunity, including the generation of durable immune memory. By dissecting how these modifications control antigen presentation pathways—particularly MHC class I and II expression—we aim to identify strategies to restore immune surveillance in aggressive cancers. Our translational goal is to leverage this mechanistic understanding to develop novel immunotherapeutic strategies. This includes designing cancer vaccines based on tumor-specific immunogenic peptides, as well as identifying small-molecule inhibitors that reverse immune evasion. Through these efforts, we aim to develop more effective, targeted, and durable immunotherapies for patients with challenging-to-treat malignancies.
Project 3: Antibody and Cell-Based Approaches to Combat Aggressive Cancers
Our laboratory is working towards developing innovative, targeted therapies for aggressive cancers that lack effective treatment options. We focus on understanding how secreted proteins in the tumor microenvironment drive cancer progression, metastasis, therapy resistance, and immune evasion. By identifying and blocking these key extracellular signals, our goal is to disrupt cancer-supporting pathways in a highly specific manner.
Our research program explores multiple therapeutic strategies:
- Antibody-based therapeutics are designed to neutralize cancer-promoting secretory proteins and block their effects on tumor growth and immune suppression.
- Antibody-drug conjugates (ADCs) deliver potent cytotoxic agents directly to cancer cells with high precision.
- CAR-T cell therapies with an emphasis on developing next-generation designs that are more specific, potent, and resistant to exhaustion, thereby enhancing their durability and effectiveness in the tumor microenvironment.
By integrating molecular biology, immunology, and structural biology approaches, we aim to advance precision medicine strategies that can provide new treatment options for patients with aggressive, treatment-resistant cancers.
