48 Gates Center research and clinician members have participated as GSIP mentors.
Below is a list of past and current mentors and a brief description of their research. Click their link to learn more.
Research in my laboratory is directed towards an understanding of the molecular and genetic mechanisms involved in the development of the neural crest. Neural crest cells are born at the neural plate border and have the extraordinary ability to retain stem cell-like characteristics. Once specified, they migrate through the embryo and give rise to a diverse array of derivatives, including peripheral neurons and glia, pigment cells and craniofacial cartilage, which form most of the vertebrate face. Thus, the neural crest is an attractive model system to study the gene regulatory networks involved in cell fate determination
Identification of melanocyte populations that emerge during NBUVB treatment of human vitiligo
Vitiligo is a depigmentation disorder characterized by white patches of the skin, the result of pigment cells loss in the epidermis. Narrow Band UVB (NBUVB) is the most effective treatment to reverse vitiligo, working by inducing in epidermis the repopulation with stem cells from the hair follicle. The current project aims to identify, in the human vitiligo skin, the melanocyte populations and their migratory, proliferative and differentiation ability augmented by NBUVB light. To accomplish this goal, biopsies from human vitiligo subjects are collected from depigmented and NBUVB-treated skin. The skin cells (melanocytes and keratinocytes) are laser capture microdissected from hair follicle and epidermis and subjected to whole transcriptome RNA sequencing or qRT-PCR, followed by gene expression analysis. The current steps of this project involve the study of the functional phenotypes induced by the top signals and pathways modulated by NBUVB. For these goals, we manipulate melanocytes and keratinocytes in culture and ex vivo skin explants."
Regulation and dysregulation of taste bud homeostasis.
Associate Director of Protein Development and Manufacturing
Gates Biomanufacturing Facility
At the GBF we collaborate with basic science and clinical investigators to successfully translate laboratory discoveries into early phase clinical trials.
Melanoma is caused by exposure to high levels of ultraviolet radiation (UVR). Susceptibility to melanoma is increased by genetic variation at a number of loci and by childhood exposures to UVR. My lab studies the skin-UVR interactions that impact on melanoma risk using both epidemiology and in vivo model systems. Our collaborative team is examining the gene-UVR interactions that give rise to melanocytic nevi in a longitudinal cohort of Colorado children that had annual data collected on nevus numbers and sizes, and on sun exposure behaviors. To date, we have identified key gene-UVR interactions that influence nevus development, and we have demonstrated that the number of sunburns and waterside vacations and the levels of chronic sun exposure experienced during childhood help to determine nevus counts. In parallel, we are studying the role of UVR in nevus and melanoma development using melanoma-prone mouse models.
The retina is a highly complex neural tissue with many distinct cell types that are each required for normal vision. How do retinal stem cells decide which cellular identity to adopt during development. The Brzezinski lab studies the molecular mechanisms that underlie retinal cell fate choice decisions. Using this developmental knowledge, the lab also investigates how stem cells can be directly programmed into retinal neurons. Since the human retina is incapable of regenerating after injury or disease, new retinal neurons generated from stem cell sources have the potential to restore vision.
Intestinal stem cell biology.
Hematopoietic stem cell development and homeostasis and leukemia; epigenetic regulation.
Cancer immunoediting is a dynamic process whereby the immune system can both constrain and promote tumor development, which proceeds through three phases termed as elimination, equilibrium, and escape. We developed a novel mouse model to capture the three phases of cancer immunoediting in vivo. The principal goal of this project is to understand the molecular mechanism underlying different stages of cancer immunoediting, including elimination, equilibrium, and escape.
Research in my laboratory focus on novel treatments for Parkinson’s disease. We were the first in the United States to transplant human dopamine neurons into a Parkinson patient. We have developed a method for reprogramming human fibroblasts to induced pluripotent stem cells using non-integrating adenoviral vectors. We have shown that these iPS cells can be generated from people with Parkinson’s disease and can be differentiated to specific cell types such as dopamine neurons and other neural phenotypes. We are also working to stop the underlying process that causes Parkinson’s disease. We’ve discovered that the drug phenylbutyrate can turn on a protective gene called DJ-1 in all neurons and can thereby prevent Parkinson’s from developing a genetic mouse model of the disease. We are planning a double-blind trial to see if the drug can stop Parkinson’s in people.
We look at the role of melanocyte stem cells and melanoma stem cells in melanomagenesis, melanoma progression, and therapeutic resistance.
Role of Endoplasmic reticulum homeostasis in bone health.
Dr. Jimeno has developed an interest in integrating preclinical research, drug development, and clinical research in Head and Neck Cancer. He holds the Daniel and Janet Mordecai Endowed Chair for Cancer Stem Cell Research. His aim is to bridge the lab and the clinic by 1) developing direct patient xenograft models of head and neck and other cancers to generate better cancer models and as a platform to study cancer stem cells, 2) conducting preclinical tests of targeted agents against de-regulated pathways and cancer stem cells, and 3) devising ways to integrate that knowledge into clinical trials to individualize anti-cancer therapy. His concomitant work in the laboratory and the clinic has materialized in the form of novel inventions (drugs and biomarkers) that are currently the subject of prospective clinical testing. He has been recognized for his research efforts with an ASCO Young Investigator Award in 2005, and two ASCO Merit Awards in 2004 and 2006. He is the author of 100 original research manuscripts, over 60 reviews, over 10 patents, and holds peer-review research from multiple organizations including the National Institutes of Health, and the Department of Defense.
Jeffrey Jacot and his collaborators are growing heart tissue using novel multilayered biomaterials and stem cells found in amniotic fluid. This tissue may one day be used to fix heart defects in infants, eliminating the need for heart transplants or multiple and complex surgeries. As director of the Pediatric Cardiac Bioengineering Laboratory at Texas Children’s Hospital and assistant professor of bioengineering at Rice University, he works alongside surgeons, clinicians, radiologists and biologists to understand the clinical needs in congenital heart defect management and repair, analyze the mechanical and biological processes in heart tissue development, and develop novel biomaterials for tissue-engineered heart muscle.
Jacot received a B.S. in Chemical Engineering from the University of Colorado at Boulder in 1994, followed by seven years of industry experience over the design and development of devices for heart surgeries. He received a Ph.D. in Biomedical Engineering from Boston University in 2005. Following postdoctoral work in the Cardiac Mechanics Research Group at the University of California, San Diego, he joined Rice University in 2008. He has received an NSF CAREER award, the Rice Institute for Biosciences and Bioengineering Medical Innovations Award and grants from the National Institutes of Health, the American Heart Association, the Virginia and L.E. Simmons Family Foundation, and the John S. Dunn foundation.
My lab research focuses on 1). Understand the role and mechanism of PI3K pathway in regulating and maintaining cancer stem cells of head and neck cancers. 2). Understand the function of disseminated tumor cells in generation of head and neck cancer recurrence and metastasis. 3). Understand the role of certain microRNAs in regulating cancer stem cells in head and neck cancers.
Breast cancer metastasis via the lymphatic system driven by normal programs of mammary gland development.
Research in the Bio-inspired Pulmonary Engineering Lab focuses on developing biomaterial-based cell culture platforms that mimic the complex structure, mechanics and composition of lung tissues and blood vessels. We design and synthesize dynamic biomaterials and use them to build cell culture systems with biomanufacturing techniques such as 3D Printing. These platforms will enable us to study the cellular and molecular mechanisms underlying chronic pulmonary diseases, including pulmonary fibrosis and hypertension and provide a foundation for the development of precision medical treatments.
Division of Pulmonary, Critical Care & Sleep Medicine
National Jewish Health
Lung Vascular Progenitors and Angiogenesis
Research taking place in the Regenerative Orthopedics Laboratory focuses on harnessing the regenerative potential of stem cells for bone and articular cartilage tissue engineering. We are particularly interested in optimizing and controlling the ability of mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs) to become bone and cartilage tissue by using different growth factors, scaffolds, and physicochemical cues. Current projects in the laboratory involve revitalizing bone allografts with stem cells to enhance bone formation, studying the effect of substrate stiffness on iPSC osteogenesis, growth plate tissue engineering, and investigating the effect of aging on the regenerative ability of stem cells.
Our lab works on ways to restore vision that has been lost due to genetics or disease. We are interested in finding ways to regenerate cells of the lens in patients with cataract, especially young people who need a clear vision for learning and working for many years to come. We also want to learn about the inherent ability of the lens to regenerate itself after surgery or trauma.
We are pre-clinical basic science lab that investigates excitability and plasticity changes that contribute to neurological deficits. Our overarching goal is to identify therapeutic strategies to improve neuronal network function that will improve neurological outcome after brain injury. We use a multidisciplinary approach that includes in vivo animal models, electrophysiology, molecular analysis of gene and protein expression and virus-mediated gene manipulation. Current projects in the lab are aimed at investigating motor and cognitive deficits after cerebellar ischemia and changes in functional connectivity of the cerebellum with forebrain areas. We also study sex- and age-dependent mechanisms that contribute to neuronal injury and plasticity deficits in the hippocampus. We are particularly interested in how sex hormones contribute to injury and repair throughout the lifespan.
Breast cancer and hormonal influences on cell state/plasticity
The Russ lab is investigating different aspects of autoimmune diabetes. Our interest ranges from identifying the molecular and cellular processes leading to disease development, to developing a treatment(s) for patients affected by diabetes. We employ state of the art pluripotent stem cell approaches, direct differentiation to generate functional cell types implicated in diabetes, genome engineering technology and organ co-cultures to generate novel model systems that provide unique biological insights in a strictly human context.
Please refer to our published work at: https://www.ncbi.nlm.nih.gov/pubmed/?term=russ+ha for more information
Dr. Shellman's research is focused on studying cancer and aging of pigment producing cells (melanocytes), and eventually to develop treatments for these health issues. This includes normal and abnormal regulation of melanocyte stem cell proliferation, differentiation and maintenance, inherited and acquired pigmentation disorders, as well as targeting melanoma stem cells as part of therapeutic development.
Translational research of heart failure and congenital heart disease using human pluripotent stem cells and rodent models
The focus of our lab is understanding how lymphatic vessels and the cells that comprise lymphatic vessels, lymphatic endothelial cells, regulate immune function and tissue homeostasis. As lymphatic endothelial cells are important both for immune cell trafficking and the drainage of interstitial fluid in every organ, these cells can have far reaching influences on a number of different systems. With that in mind we focus on how lymphatic endothelial cells react and program the immune system during immune insults such as viral and bacterial infections, immunization, chronic inflammation and cancer.
My laboratory is interested in the regulation of a key tumor suppressor, the transcription factor p53. p53 is mutated in over 50% of human cancers and has therefore been the subject of intensive basic and preclinical investigation. In the hope of improving cancer therapies that specifically target p53 mutations, we are investigating the role of different p53 mutations in driving tumorigenesis. For this, we are using novel combinations of extant mouse models of cancer, murine xenografts, and sophisticated tissue culture systems.
Our main focus is to understand how mitotic proteins such as Aurora Kinase A can control epithelial stem cell function in development and tissue homeostasis and are altered in proliferative diseases such as cancer. We utilize in vivo cancer models and tissue culture based systems to explore this question and ways of exploiting abnormal mitosis in disease as a therapeutic strategy.
Our lab studies how the innate immune response dictates healing, repair, or scarring of the injured heart. We are currently focused on the role of cardiac tissue macrophages and are exploring ways to optimize the cellular responses of innate immunity for tissue healing and regeneration.
The overarching goal of the Verneris laboratory is to create new targeted immune therapies to treat cancer in children and adults. Our laboratory is focused on using stem cells to create “off the shelf” living drugs to treat cancer and other diseases. To do this we use hematopoietic stem cells and induced pluripotent stem cells to understand how these cells give rise to natural killer (NK) cells and T cells. Thus, our research is in two broad areas:
Stem Cell Biology: We seek to understand how stem cells can be expanded and manipulated to differentiate into lymphocytes. We work with established embryonic and induced pluripotent stem cells, as well as hematopoietic stem cells derived from cord blood and bone marrow. Our studies are focused on stem cell biology and differentiation into the lymphocyte lineage (including NK cells, T cells, and innate lymphoid cells).
Lymphocyte Biology: We have focused on redirecting the immune system to cancer. Studies include the use and development of bi- and trispecific immune killer engagers (BiKes and TriKes) and chimeric antigen receptors (CARs). We have also discovered a how to differentiate stem cells to innate lymphoid cells and natural killer cells. We are using drugs and genetic screens to enhance this process and genetic manipulation to increase their activity and homing into solid tumors (sarcoma and brain tumors). The long term goal is to have an “off the shelf” living drug that can be used to mitigate graft vs. host disease, inflammatory bowel disease and cancer.
My research efforts are focused on understanding the molecular mechanisms of heart failure, a complex, multifactorial syndrome characterized by both cardiac and systemic disturbances. It is clear that an insult – whether environmental or genetic – triggers a multitude of changes at the cellular level that ultimately result in organ level dysfunction. We use a number of models in order to address these changes on the cellular level, focusing on proteomic differences (translational and post-translational) in the dysfunctional heart. These models include a mouse myocardial infarction model, a genetic model that mimics heart disease in males and a genetic model that predominantly affects females, as studies show there is a disproportionate impact on women with regard to health consequences from heart failure. Additionally, collaborative efforts allow us to study a large animal (bovine) model of right heart dysfunction and other collaborations with the surgeons at the University of Colorado Hospital provide access to human heart samples – allowing elucidation of relevant pathways in human cardiac tissue. Together these models provide a platform for identifying the proteomic changes underlying cardiovascular disease and in describing the sexually divergent pathways cardiac maladaptation in women.
Our research is focused on the identification of cancer stem cells in head & neck cancer and skin cancer; and then studying stem cell fate decisions during skin development and cancer.
Applications accepted now through February 6th for the Class of 2023!