Stem cells

Curtis Thorne

Associate Professor, Cellular and Molecular Medicine
Assistant Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Contact
(520) 626-0395

Work Summary

We combine chemical and computer vision approaches to discover how regenerative tissues process environmental information to promote accurate cell fate decisions and prevent uncontrolled cell growth.

Research Interest

We study control of cell fate and self-organization in intestinal renewal and drug response in cancer. Utilizing the fascinating characteristics of intestinal stem cells combined with chemical biology and computational image analysis approaches, we are addressing fundamental questions of multicellular systems: How do cells identify, measure, and respond to each other and to their environment? What are the signals that control the renewal and regeneration of tissues? How do these signals become defective in colorectal cancer? Our long-term goal is to uncover an underlying circuit theory behind these behaviors – a set of predictive principles that tell us how complex functionality arises from simpler biological components. We have a particular interest in kinase networks that regulate healthy tissue homeostasis and become damaged in cancer. Through our quantitative high-throughput imaging and drug discovery efforts, we are finding new ways to understand and repair these networks. Keywords: Stem cells, Cancer, Regeneration, Drug discovery

Frans E Tax

Associate Dean, Student Affairs, Diversity & Inclusion
Distinguished Outreach Professor
Professor, Molecular and Cellular Biology
Professor, Plant Sciences
Professor, Applied BioSciences - GIDP
Professor, Genetics - GIDP
Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Contact
(520) 626-1186

Research Interest

Plants grow as a result of the proliferation of stem cells and the establishment and maintenance of defined developmental fates in progeny cells. Our major goal is to elucidate general molecular mechanisms used by plants to specify and maintain cell fates, ranging from stem cells to fully differentiated cell types. Both experimental manipulations and the identification of genes responsible for the maintenance of stem cells and for the establishment and maintenance of differentiated cell fates through forward genetic screens implicate intercellular signaling in these processes. Because of the important role of intercellular signaling in the differentiation of cells initiating from meristems, studying receptors is one way to dissect these molecular mechanisms. To understand signaling events that take place in development, we analyze the phenotypes of plants mutant for individual or multiple receptors. My lab has identified key roles for specific receptors during radial patterning in early embryogenesis (Nodine et al., 2007), during the formation of lateral roots (Wierzba and Tax, in preparation), in the formation of fruit organs from stem cells within the fruit (Durbak and Tax, 2011), in the development of vascular tissues (Bryan et al., 2012), and in the process of cell elongation (Li et al., 2002). Future studies will include further analysis of the signaling networks anchored by these receptors, with a specific focus on the transitions between different downstream transcription factor targets. In addition, we are interested in developing approaches to isolate mutants in these receptors to manipulate the architecture and physiological responses of crop plants.

Lalitha Madhavan

Associate Professor, Neurology
Associate Professor, Medicine
Associate Professor, Neuroscience - GIDP
Associate Professor, Molecular and Cellular Biology
Associate Professor, Evelyn F Mcknight Brain Institute
Associate Professor, Clinical Translational Sciences
Associate Professor, Physiological Sciences - GIDP
Associate Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-2330

Research Interest

Dr. Madhavan M.D., PhD, is an Assistant Professor of Neurology at the University of Arizona. She is also a member of the Arizona Cancer Center and the Evelyn F. McKnight Brain Institute, and is affiliated with the Neuroscience, Physiology and Molecular, Cellular Biology graduate programs at UA. Dr. Madhavan’s research centers on stem cells and neurological diseases. The ultimate goal of the work is to devise brain repair strategies for neural disorder using stem cells, and other alternate approaches. Currently, her lab is focused on Parkinson’s Disease, and is engaged in three main endeavors: (1) Understanding the therapeutic potential of stem cells in the context of aging, (2) Creating patient-specific induced pluripotent stem cells to study the etiology of Parkinson’s Disease, and (3) Testing the therapeutic feasibility of various types of adult stem cells in preclinical Parkinson’s Disease models. These projects are united by a common goal, which is to investigate core problems hindering the development of effective stem cell-based therapies for Parkinson’s Disease. In addition, the work represents a novel path of research for not only Parkinson’s Disease therapy, but has broad implications for developing treatments for several other age-related neurodegenerative disorders. Visit the Madhavan Lab website to learn more.

David T Harris

Executive Director, AHSC Biorepository
Professor, Immunobiology
Professor, Medicine
Professor, Applied BioSciences - GIDP
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-5127

Work Summary

We are involved in banking clinical specimens obtained from various patients for use in biomarker discovery and clinical therapies. Clinical therapies may include regenerative medicine, transplant or gene therapy.

Research Interest

David Harris, PhD, occupies research efforts directed at the application of (cord blood and adipose) stem cells to transplantation, regenerative medicine and tissue engineering. The difficulty in locating bone marrow donors for patients needing transplants, particularly for minority patients, led to the investigation of other potential sources of stem cells. One such source that has become a viable alternative to bone marrow is umbilical cord blood. Not only has the use of cord blood allowed more patients to go to transplant due to less restrictive matching requirements between donor and recipient, but cord blood transplants are associated with fewer post-transplant complications, such as a lower incidence and severity of graft-versus-host disease (GVHD). In 1989, he began work on the use of cord blood for transplantation, which led to the establishment of the first cord blood bank in the United States in 1992, which is currently the largest such establishment in existence. Work continues today using animal models for cord blood transplantation to explore such research areas as graft-versus-leukemia, GVHD, regenerative medicine and tissue engineering applications. However, studies performed in his lab examining the use of cord blood stem cells in regenerative medicine is now our major emphasis. Work in regenerative medicine has focused on several specific areas of interest. The first area is the use of stem cells in an ischemia/reperfusion injury model of myocardial infarction in a rat model, with positive results. Efforts are underway to understand the molecular mechanisms involved and to derive small molecule drugs in collaboration with Dr. M. Gaballa at Sun Health Research Institute. Secondly, Dr. Harris has been successful in deriving epithelial tissues in vitro that mimic corneal tissues, both morphologically and histologically. When transplanted in vivo in rabbits, the tissues are equivalent to cadaver corneas in terms of sight restoration and function. Dr. Harris and his team are currently developing a human-to-human eye model that will avoid some of the xenogeneic complications associated with the rabbit model, in conjunction with the Dept. of Ophthalmology.Third, they have successfully derived glial, astrocyte and oligodendrocyte cell types from cord blood stem cells in vitro. Currently, these cells are used to study pediatric HIV infection at the molecular level, but are also amenable to work in Parkinson’s and spinal cord injury models. Dr. Harris is now collaborating with Dr. Madhavan of Neurology to study Parkinson’s disease and with Dr. Rogers of Stanford Research Institute to study Alzheimer’s disease. Fourth, recent work has begun comparing various stem cells sources (cord blood, bone marrow and adipose tissue) for the capacity to be used in regenerative medicine. Finally, over the past year they have investigated the use of cord blood stem cells for epithelial wound healing, with the goal being the treatment of non-healing wounds and ulcers in diabetic and bed-ridden patients. It has been found that injections of bone marrow stem cells, both intravenously as well as in the wound margins, significantly reduce healing time as well as minimizing scar formation. Of interest, the age of the recipient plays a significant role in wound healing. Keywords: stem cells, regenerative medicine, biobanking

Steven Goldman

Professor, Medicine - (Research Scholar Track)
Research Scientist
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-2939

Work Summary

Our lab has a new treatment for heart failure. We have a biodegradable graft seeded with adult human cells that we put on the surface of the heart. The potential is to regenerate new heart muscle

Research Interest

Research in my laboratory over the last 30 years has focused on chronic heart failure (CHF), its pathophysiology and the development of new treatments for CHF. We have developed clinically relevant animal models of heart failure that allow us to explore the translational potential of new treatments. Our work initially examined the role of afterload reduction and neurohormal blockade. More recently we have been working with cell-based therapy for CHF using bioengineered scaffolds to prevent left ventricular (LV) remodeling and restore function in the damaged heart. Our most effective scaffold is a biodegradable vicryl mesh with embedded viable neonatal fibroblasts that secrete angiogenic growth factors. This patch increases myocardial blood flow, improves LV systolic function, and reverses LV remodeling if implanted at the time of an acute myocardial infarction. In CHF, this patch still improves myocardial blood flow but does not improve LV function or reverse LV remodeling. Thus, we have an effective delivery system for cell based therapy for CHF that increases myocardial blood flow and provides structural support for new cell growth. We are now focusing on seeding this patch with human inducible pluripotent stem cells in the cardiac lineage, the seeded cardiomyocytes align, communicate, contract in a spontaneous and rhythmic fashion. When implanted in rats with CHF, they improve LV function. We are exploring this patch seeded with human inducible cardiac pluripotent stem cells to treat patients with CHF. Keywords: induced pluripotent stem cells

Deepta Bhattacharya

Professor, Immunobiology
Professor, Surgery
Professor, Cancer Biology - GIDP
Professor, Genetics - GIDP
Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
(520) 626-8088

Research Interest

Research in the Bhattacharya lab focuses on molecular approaches to direct B cell differentiation to establish immunity to infectious disease, and stem cell differentiation for regenerative medicine. Current projects in the lab include: 1) Understanding the cellular basis of antibody-mediated immunity to variable viruses. After infection or vaccination, B cells that recognize the pathogen proliferate and undergo a massive level of expansion. Upon clearance of the infection a small fraction of the "best" B cells are retained to become memory B cells or long-lived plasma cells. Our recent work has established that memory B cells are excellent at recognizing not only the original pathogen, but also mutant escape variants of the pathogen. In contrast, long-lived plasma cells are highly specific only for the original pathogen. We are studying the transcription factors that regulate the memory B cell vs. long-lived plasma cell fate, and are studying mechanisms to alter this fate to provide effective immunity against mutable viruses such as influenza and Dengue. 2) Identifying molecular regulators of the duration of immunity. Most clinically used vaccines rely on the production of antibodies to confer immunity. The duration of immunity can vary greatly between different vaccines, yet the molecular basis of this remains unknown. Current efforts are focused on the identification of genes that regulate plasma cell lifespan and on the features of the vaccine that confer durable antibody immunity. 3) Engineering human pluripotent stem cells to generate antibody-mediated immunity. A small fraction of patients infected with HIV or dengue virus, or vaccinated against influenza develop remarkable antibodies that neutralize nearly all clinical isolates of these viruses. Yet it is unclear how to induce these types of antibodies in the broader population through standard vaccination. Using novel targeted nuclease technologies, we are engineering human embryonic stem cells to express these antibodies and differentiating them into transplantable long-lived plasma cells. The long-term goal of this project is to provide permanent immunity to recipients of these engineered plasma cells.