48 Gates Institute 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.
The goal of our lab's research program is to unravel the genetic and molecular basis of splicing factor gene mutations in clonal hematopoiesis and myeloid malignancies, such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).
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
My lab is focused on testing the pro-melanogenic and pro-proliferative effects of three phosphodiesterase 4 inhibitors (PDE4i) compounds on 2 in vitro model systems: normal human melanocyte cultures and Melanoderm (a three-dimensional tissue culture model of human epidermis that contains normal human melanocytes and keratinocytes). We would like to better understand the mechanism of action of PDE4 inhibitors, that we test in parallel in vitiligo patients.
Regulation and dysregulation of taste bud homeostasis.
Associate Director of Protein Development and Manufacturing
Gates Biomanufacturing Facility
Biomanufacturing - Protein Development
The Biologics Development and the Manufacturing Team collaborates with applied science and clinical investigators to successfully translate investigational discoveries into early phase clinical trials. Our Team works on Technology Transfer, Process Development and Large-Scale manufacturing Biologics, including but not limited, recombinant protein expressed in E. coli, nanoparticle conjugates and mRNA. In addition, we work on analytical assay development of biologics screening, HPLC, DSL, MWD etc.
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.
Kristen E. Boyle, PhD
Associate Professor Pediatrics
We know that health and exposures during pregnancy, such as obesity, diabetes, and environmental pollutants, can increase the child’s risk for later disease. In our lab, we study molecular metabolism in stem cells from infant umbilical cord to identify factors that may predispose children to developing obesity or diabetes later in life following various exposures in utero.
My lab studies how mammalian retinas (mouse and human) develop. In particular, we investigate how gene regulatory networks control cell fate choice during development. We are also using our knowledge of retinal development to help design cell-based therapies for blinding diseases.
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.
The long-term goal of the research carried out by my team is to contribute to a better understanding of the early events involved in early Age-related Macular Degeneration (AMD). Dry AMD begins with the appearance of drusen, and the lack of therapies responds, to a certain extent, to our little understanding of drusen formation. To overcome this problem, my studies seek to understand how little vesicles, called exosomes, secreted by RPE and containing lots of cellular bioproducts, are delivered from unhealthy RPE and contribute to drusen formation and AMD progression. We mimic dry AMD disease using RPE cells derived from stem cells and recapitulate AMD mechanisms, including drusen formation. Under healthy conditions, exosomes secreted by RPE cells are enriched in proteins associated with mechanisms involved in AMD pathophysiology. Remarkably, exosomes secreted by RPE within an AMD environment significantly increased the release of well-known proteins associated with AMD that are all crucial in drusen formation. We provided evidence for a possible active role of exosomes released by RPE in drusen biogenesis. Furthermore, due to the exosome capacity to travel through different biofluids and since their cargo changes under pathological conditions, exosomes could give us the key to diagnosing AMD early and successfully treating it.
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.
Bioengineering, Pulmonary Sciences and Critical Care Medicine
We engineer 3D models of lung tissue to help the world breathe easier. Research in the Bio-inspired Pulmonary Engineering Lab focuses on engineering biomaterial-based cell culture platforms that mimic the complex structure, mechanics and composition of lung tissues and blood vessels.
Division of Pulmonary, Critical Care & Sleep Medicine
National Jewish Health
Lung Vascular Progenitors and Angiogenesis
Gates Biomanufacturing Facility – Cellular Therapies
At the GBF we collaborate with basic science and clinical investigators to successfully translate laboratory discoveries into early-phase clinical trials. Using a variety of analytical techniques, my team develops the assays used to demonstrate a product is what it should be, does what it should do, and is safe to administer to patients.
Glaucoma is the second leading cause of blindness worldwide and characterized by progressive loss of retinal ganglion cells. Dr. Mi-Hyun Nam has been developing a gene or peptide-based therapy for rescuing retinal ganglion cells in mouse models of glaucoma.
Prof. Nagaraj’s laboratory investigates the biochemical mechanisms of secondary cataracts, presbyopia and glaucoma, and develops gene and small molecule-based methods to prevent vision loss from those diseases/abnormalities.
Our research focuses on the development of regenerative medicine approaches for bone and cartilage tissues, with a particular interest in treating growth plate (physeal) cartilage injuries, which represent a significant clinical problem in children. Growth plate injuries can result in the formation of unwanted bony repair tissue across the cartilaginous growth plate, known as a “bony bar”. This bony bar can restrict local growth, leading to significant growth abnormalities, such as angular deformities or complete growth arrest. Our laboratory studies biomaterial-based approaches to prevent the bony bar formation and regenerate the growth plate cartilage. These activities also include the development of a 3D printed pediatric growth plate mimetic composite. Therapies are tested in vitro, as well as in animal models of growth plate injury.
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.
My lab focuses on the early events that trigger evolution to malignancy in blood-forming hematopoietic stem cells, with particular interest in the interplay between chronic inflammation and mutation-induced changes in stem cell metabolism that drive malignant progression. We also perform 'bench to bedside and back' translational investigations evaluating the impact of novel therapeutics in eradicating malignant stem cells in order to identify new therapies that can comprehensively eliminate these cells in patients with myelodysplastic syndrome, a malignant blood disorder that can evolve into leukemia.
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.
Our lab specializes in translational research on multiple myeloma, a debilitating and incurable blood cancer. We are focused on developing new therapies, including both large-molecule immunotherapies and small-molecule pathway inhibitors. In parallel, we are developing an approach to personalize treatment through real-time monitoring of drug resistance development using ex vivo drug sensitivity testing.
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 have closed for the class of 2023. Check back in December for information on applying for the class of 2024.