Research

Hematologic Malignancies and Blood Disorders

In the Huang Lab, one of our primary research areas is the study of blood cancers and disorders, such as myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), and acute leukemia. These diseases affect the blood and bone marrow, leading to severe health complications and significantly impacting patients’ quality of life.

We investigate how genetic and epigenetic factors, along with signaling pathways, regulate the functions of hematopoietic stem cells—the cells responsible for generating all blood cell types. Understanding how these cells maintain a delicate balance between self-renewal and differentiation is crucial, as disruptions can lead to the development of malignancies.

Our research has highlighted the crucial role of mitochondrial metabolism in these diseases. Mitochondria, often referred to as the powerhouses of the cell, play a vital role in energy production and metabolic regulation. We have discovered that alterations in certain metabolic enzymes within the mitochondria, such as components of the succinate dehydrogenase (SDH) complex, can contribute to the development and progression of MDS. These findings suggest that metabolic dysfunction is a key driver of disease pathology.

By understanding these metabolic changes, we aim to develop new therapies that target these pathways, offering hope for patients who have limited treatment options. Our approach includes:

• Developing Genetically Distinct Mouse Models: We create animal models that closely mimic human disease, allowing us to study the effects of specific gene alterations in a controlled environment. These models are invaluable for testing potential therapeutic interventions before moving into clinical trials.
• Exploring Mitochondrial Metabolism and α-KG–Dependent Dioxygenases (2OGDDs): We are investigating how mitochondrial dysfunction affects enzymes that regulate epigenetic modifications. This research could reveal new ways to reverse abnormal gene expression patterns in cancer cells, restoring normal function and preventing disease progression.
• Translational Research: Our discoveries are paving the way for clinical research targeting SDH genes. By collaborating with clinicians, we aim to translate our findings into new therapies for MDS patients worldwide.

Moreover, our work has broader implications for other types of cancers, such as lymphoma, renal cell carcinoma, and glioma, where dysregulated mitochondrial metabolism plays a critical role. By extending our research to these areas, we hope to make a wider impact on cancer treatment.

Solid Tumor Therapies and Immunotherapy

Another significant focus of our lab is the development of novel treatments for solid tumors, which are often resistant to conventional therapies like chemotherapy and radiation. Solid tumors, such as liver cancer (hepatocellular carcinoma) and melanoma, present unique challenges due to their complex microenvironments and ability to suppress immune responses.

We are exploring innovative approaches using Chimeric Antigen Receptor (CAR) T-cell therapy. This cutting-edge immunotherapy involves modifying a patient’s own immune cells to recognize and attack cancer cells more effectively. While CAR T-cell therapy has shown success in treating certain blood cancers, its application to solid tumors has been limited due to challenges like:

• Tumor Immune Microenvironment (TIME): Solid tumors often create a hostile environment that inhibits immune cell function. The TIME can suppress immune responses and promote tumor growth.
• Physical Barriers: Dense tissue and abnormal blood vessels can prevent immune cells from reaching the tumor core.

Our lab is pioneering the use of CAR T-cells as a specialized delivery system to target the TIME. By engineering CAR T-cells to not only recognize cancer cells but also modulate the surrounding environment, we aim to enhance their ability to penetrate tumors and sustain their activity within this hostile setting.

Key aspects of our approach include:

• Next-generation CAR T-cells: We are designing CAR T-cells to deliver therapeutic agents directly into the tumor site, disrupting the protective barriers that shield cancer cells.
• Targeting Metabolic Pathways: By understanding how tumors alter metabolism to suppress immune responses, we can modify CAR T-cells to overcome these metabolic hurdles.
• Enhancing Persistence and Efficacy: Our goal is to create CAR T-cells that can survive longer within the tumor environment and maintain their cancer-killing functions.

This innovative therapy represents a significant advancement in the field and holds promise for treating cancers that have been traditionally difficult to manage. Our patented strategies are at the forefront of precision immuno-oncology, aiming to bring more effective treatments to patients in need.

Cancer-Associated Cachexia

Cancer-associated cachexia (CAC) is a debilitating condition characterized by extreme weight and muscle loss, affecting many cancer patients and significantly impacting their quality of life. This syndrome not only diminishes patients’ physical strength but also interferes with their ability to tolerate treatments, ultimately affecting survival outcomes.

In our lab, we are investigating the metabolic disturbances that lead to cachexia. Our goal is to identify the underlying mechanisms, such as inflammatory cytokines and metabolic imbalances, that drive this syndrome. We are exploring how tumors communicate with distant organs, triggering systemic effects that result in muscle wasting and fat loss.

Our research focuses on:

• Identifying Novel Biomarkers: By discovering molecules that indicate the onset or progression of cachexia, we can develop diagnostic tools for early detection.
• Understanding Metabolic Perturbations: We study how cancer alters normal metabolism, leading to energy deficits and tissue breakdown.
• Developing Therapeutic Targets: By pinpointing key pathways involved in CAC, we aim to create interventions that can prevent or mitigate its devastating effects.

Our work in this area is highly interdisciplinary, combining expertise in cancer biology, metabolism, immunology, and clinical nutrition. We collaborate with clinicians to translate our findings into clinical trials, with the hope of improving patient well-being and treatment success.

Translational Research and Collaboration

We believe that collaboration is key to advancing cancer research. The Huang Lab works closely with clinical researchers, other academic institutions, and industry partners to translate our scientific discoveries into real-world applications. Through these partnerships, we strive to bring innovative therapies from the bench to the bedside, ultimately making a tangible difference in the lives of cancer patients.

Our commitment to translational research involves:

• Clinical Trials: We actively participate in designing and conducting clinical trials to test new therapies developed in our lab.
• Industry Partnerships: Dr. Huang has founded Powerhouse Therapeutics Inc., a biotechnology company dedicated to advancing our lab’s inventions and bringing them to the market. This venture bridges the gap between research and patient care.
• Educational Outreach: We provide opportunities for students at the undergraduate, graduate, and postdoctoral levels to engage in cutting-edge research. By fostering a nurturing environment that encourages curiosity and innovation, we aim to train the next generation of scientists.

Our numerous publications in high-impact scientific journals reflect our lab’s dedication to excellence and our contributions to the field of oncology. Dr. Huang has published over 100 papers in prestigious journals, including Nature, Cancer Discovery, Molecular Cell, Nature Genetics, and Journal of Clinical Investigation.

We remain steadfast in our efforts to understand cancer from every angle and to develop solutions that can change the course of this disease. Our lab is not just a place of research; it’s a community dedicated to making a difference.

We invite you to explore our research further, learn about our current projects, and consider how you might join us in our mission. Whether through collaboration, support, or simply sharing our vision, your involvement can help us make significant strides in the fight against cancer.