Biomedical research in the NSU Cell Therapy Institute is centered around cell-based advanced therapies for cancer, cardiovascular disease, and degenerative diseases. The therapeutic approaches involve modifying immune cells for immunotherapy or developing stem cells for regenerative medicine. This research is complemented by cutting-edge genomics, recombinant DNA, flow cytometry, and cellular imaging technologies. The ultimate goal of research at the Institute is to help transform the future practice of medicine with safer and more effective therapies.
Examples of immunotherapy research in the NSU Cell Therapy Institute include genetic modification of immune cells so they are able to more aggressively seek out and destroy cancer cells wherever they may be hiding in the body. Another approach to cancer immunotherapy involves immune cell activation using biological molecules such as cytokines to reverse immune evasion by cancer cells in the tumor microenvironment.
In the area of regenerative medicine, researchers in the Institute are focused on development of stem cell therapies to repair damaged heart and valve tissues. This involves differentiation of stem cells into heart muscle and blood vessel cells in vitro to replace the damaged cells in vivo. Additional stem cell research is aimed at reversing macular degeneration, a major cause of blindness among the elderly, and neurodegenerative diseases including amyotrophic lateral sclerosis (ALS).
Richard Jove, Ph.D., is director of the NSU Cell Therapy Institute and provides overall scientific leadership. The Institute’s mission is to extend life and enhance human health by urgently advancing innovative biomedical research discoveries, leading to better treatments, improved outcomes and durable cures. This translational research goal is greatly enhanced through international collaboration with medical scientists from Karolinska Institutet, Stockholm, Sweden. Below are summaries of NSU Cell Therapy Institute research projects and the collaborating principal investigators.
The goal of “regenerative medicine” is to restore structure and function of damaged tissues and organs resulting from injuries or diseases. Cardiovascular disease is a leading cause of mortality for which there are limited treatment options such as heart transplants. Therefore, innovative approaches, including therapeutic stem cells, are needed to replace damaged cells and tissues. Clinical studies have investigated cell therapy for regeneration of heart muscle with varying levels of success and the most optimal cell types for cardiac repair remain to be determined. The cardiac research unit is led by Vladimir Beljanski, Ph.D., assistant professor at NSU, in collaboration with Karl-Henrik Grinnemo, M.D., Ph.D., visiting research professor from Karolinska Institutet, to develop multipotent stromal cells for repair of heart muscle after cardiac infarction. Grinnemo is a cardiac surgeon investigating new clinical strategies for treatment of cardiac diseases with therapeutic stem cells. Beljanski is a basic scientist involved in mechanistic studies and testing therapeutic efficacy of cardiac progenitor cells using pre-clinical models of heart failure.
The NSU Cell Therapy Institute team is utilizing multipotent stromal cells isolated from either hearts or umbilical cords and differentiating them into three types of cardiac cells: cardiomyocytes, endothelial cells, and stromal cells. These cells are then evaluated for their capacity to downregulate immune responses and restore normal function of damaged heart muscle. In addition, genomics approaches that utilize RNA-sequencing and ex vivo approaches that evaluate stress response in therapeutic efficacy of cells are utilized to determine optimal cell types for cardiac repair and understand how such cells respond to their microenvironment. Results of these studies will help lay the foundation for improved cardiac therapies based on regenerative medicine.
The vascular biology unit is led by Cecilia Osterholm Corbascio, Ph.D., visiting research professor from Karolinska Institutet. She is an expert in molecular biology of cardiovascular diseases and is studying the mechanisms for development of aortic valve stenosis, which is a leading cause of death in the U.S. The molecular process includes activation of valvular interstitial cells, inflammation and altered extracellular matrix composition, which results in increased stiffness and calcification of the valvular leaflets. Current treatment for aortic valve stenosis is replacement of the diseased tissue with mechanical or biological prosthetic valves, which entails the risk of lifelong treatment with anticoagulants for the former, or rapid degradation in case of the latter. This project aims to unravel the molecular events of the disease process from the perspective of the valvular extracellular matrix. Knowledge gained from these studies will help to understand how the disease is initiated and progresses and provide an important basis for the development of functional, long-lasting bioprosthetic valves using de-cellularized scaffolds and mesenchymal stem cells.
Cancers have evolved multiple mechanisms to suppress the immune system and avoid detection. Therapies for cancers that enhance the immune system to specifically target cancerous cells are collectively called “cancer immunotherapies” and have shown promising results for many cancer types. Despite the recent success in these cancer immunotherapies, many patients still suffer from their disease. Increasing evidence supports the idea that cells within the growing tumor, i.e., the tumor microenvironment, suppress the immune system and limit the efficacy of cancer immunotherapy. The cancer immunology unit is led by Shannon Murray, Ph.D., assistant professor at NSU in collaboration with Andreas Lundqvist, Ph.D., visiting research professor from Karolinska Institutet. The focus of this research is to develop more effective cancer immunotherapies that reverse immunosuppression. Murray examinesthe basic immunology of cancers and how HIV infections increase the risk of certain cancers.
The team has characterized how certain cells within the tumor microenvironment suppress the immune system. Their current research focus is to gain a deeper understanding of how these cell populations can be selectively targeted to improve reconstitution of an effective anti-tumor immune response for multiple cancer types, including melanoma and renal cell carcinoma. Ongoing projects in the laboratory involve targeting specific cell populations in the tumor microenvironment including dendritic cells and myeloid-derived suppressor cells. Another key research area is to understand how the immune system, in particular, tumor-reactive T and natural killer (NK) cells, can be rendered resistant to immunosuppressive mechanisms within the tumor microenvironment.
This research group recently identified novel gene-expression programs in NK cells with the ability to resist tumor-induced immunosuppression. The group is currently pursuing these findings to create populations of activated NK cells with optimal anti-tumor activity to be used as cancer therapies. The team works on the premise that if tumor-induced immunosuppression can be reduced, then more effective cancer immunotherapies can be delivered to patients with metastatic cancers. The collaboration with the Karolinska Institutet laboratories allows for a bench-to-bedside approach, which connects the basic scientific research with research that focuses directly on translation to the clinic. These studies will advance our understanding of cancer immunology and facilitate the development of more effective immunotherapies for cancers.
A group of researchers in the NSU Cell Therapy Institute are mainly focused on the fields of immunotherapy and regenerative medicine, with the goal to develop cell-based therapeutic approaches to treat cancer and age-related degenerative diseases. The cancer immunotherapy unit is led by Adil Duru, Ph.D., NSU assistant professor, in collaboration with Evren Alici, MD. Ph.D., visiting research professor from Karolinska Institutet. The research group is focusing on optimizing stem cell-derived natural killer (NK) cell differentiation and expansion platforms to develop innovative NK cell-based immunotherapies for cancer treatment. Additionally, this team investigates the interactions of NK cells with the tumor stroma and the impact of these interactions on NK cell development and function in an in vitro model. Furthermore, the research group also aims to develop efficient gene delivery methods for NK cells in order to enhance the applicability of genetically modified NK cells for cancer treatment. The ultimate goal of this research is to generate NK cells that are activated and specifically targeted to efficiently detect and eliminate cancer cells.
The degenerative diseases unit is led by Outi Hovatta, M.D., Ph.D., a visiting research professor from Karolinska Institutet. Hovatta uses her expertise gained as a professor in obstetrics and gynecology to bridge the gap between early human developmental biology and regenerative medicine. This research team focuses on establishing xeno-free, serum-free and fully defined stem cell processing methodologies for clinical applications developed under cGMP conditions. Hovatta is pioneering stem cell therapy for macular degeneration, the leading cause of blindness for elderly persons, among other degenerative diseases. The curative strategy involves transplanting stem-cell derived retinal pigment epithelial cells directly into patients’ eyes to regenerate the retina and restore vision. This team is also investigating novel ways to overcome the issue of transplant rejection, which is a major hurdle to realizing the full potential of stem cell therapies. The team is also conducting collaborative studies in the area of neurodegenerative diseases with a goal of developing novel regenerative medicine treatments for various neurodegenerative diseases.including amyotrophic lateral sclerosis (ALS).
This research team is focused on molecular and surgical oncology in solid tumors. Thomas Temple, M.D., NSU’s senior vice president of translational research and economic development and professor of orthopaedic surgery is researching novel targeted therapies in sarcomas, cancer stem cells, and bone regeneration. In addition to his interests in surgery, molecular mechanisms and targeted therapies for sarcomas, Temple’s principal focus is to translate research discoveries into clinical trials and establish an international center of excellence at NSU to achieve this goal. Johannes Vieweg, M.D., founding dean of NSU’s College of Allopthic Medicine (M.D. College) and professor of urology is is focused on developing new cellular immunotherapies for the treatment of prostate cancer, including cancer stem cells. Vieweg is establishing the new M.D College at NSU using an innovative curriculum that integrates research into medical education and patient care. Richard Jove, Ph.D., institute director and NSU professor, is a molecular oncologist with a research interest in novel combinations of molecular and cellular therapies targeted against cancer stem cells. His research involves single cell genomics and small molecule drug discovery approaches. This team has complementary strengths in different aspects of precision medicine strategies for safer and more effective cancer treatments.