CSTR Pilot Grant Program

The overall goal of the CSTR Pilot Grant Program is to provide the infrastructure for catalyzing innovative, high risk/high gain interdisciplinary and collaborative clinical and translational research projects. Emphasis will be on developing novel approaches and methodologies for cost-effective execution of research projects and testing feasibility of novel approaches for conducting clinical and translational research. The Pilot Grants are expected to invigorate the clinical and translational research environment and enhance the potential for competitive multi-investigator grant applications to the NIH. This program has generated enthusiastic participation and has stimulated novel interdisciplinary collaborations that might not otherwise occur.

This program

  • Develops the infrastructure and mechanisms to fund and implement processes for soliciting, evaluating, awarding, mentoring, and tracking pilot projects that support transformative clinical and translational research.
  • Trains and mentors new and less experienced investigators in clinical and translational research
  • Ensures the success of funded pilot research through mentoring from experienced investigators, project monitoring by Translational Pilot Program leaders, and assets from the CSTR Institute.

New Pilot Grant Opportunities

Proposals are now being accepted for the 2018 Clinical Science & Translational Research (CST*R) Institute Pilot Grant Program. Each Pilot Grant must have three TAMU co-PI’s and will provide $100,000 ($25,000 from CST*R plus $25,000 matching from each of the three TAMU co-PI’s academic units) for a period of one year for supplies and salaries for trainees and technical staff. Faculty salaries, equipment, travel, and indirect costs are not allowable expenses under this program. The application process will involve a pre-proposal review and selected applications will be eligible to submit a full proposal for funding review.

CST*R Pilot Grants are intended to provide funds for the generation of sufficient scientifically meritorious data to enable submission of a proposal to federal agencies or private foundations to support work that emphasizes multi-investigator clinical and translational interdisciplinary research.

Detailed instructions can be found in the Guidelines

Questions may be directed by e-mail or by phone to 713-677-8115.

Active Research Projects

1. Ensuring Dogs Remain Man’s Best Friend – Understanding how Staphylococcus pseudintermedius Infects People and Dogs (2018) 

The primary goal of this project is to build on the momentum we have with our characterization of Staphylococcus pseudintermedius (SP) and methicillin-resistant SP (MRSP) to generate the preliminary data required for a competitive NIH R01 grant proposal. We propose that SP strains that colonize dogs likely give rise infections in the animals. Within these colonizing strains there is significant sequence variation within individual secreted and cell wall associated (CWA) proteins. Through selection and opportunity, these colonizers cause both wound infections and disseminated infections. The virulence factors associated with wound infections likely differ with those required for survival in the blood and dissemination to sites of infection throughout the body (e.g. bone, heart, etc.). The same is expected for SP isolates from human infections although SP moving from its natural host the dog to humans now require virulence factors that can interact with targets also in the new host; man. The SP virulence factors required for human wound infection likely differ from those required for bacteremia and disseminated infection and probably represent a subset of those engaged in the corresponding infections in the dog. Understanding and documenting which sequence types (STs) of SP strains causing disease in people and understanding the virulence factor sequence variation that occurs in human and canine SP from wounds and disseminated infections is critical in developing a compelling R01 proposal to NIH.

  • Magnus Höök, PhD,(PI) Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center
  • David Threadgill, PhD, (Co-PI) Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University
  • Sara Lawhon, DVM, PhD, (Co-PI)Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
  • Robert Fader, PhD, (Co-PI) Department of Microbiology, Baylor Scott & White Health
  • Arthur Laganowsky, PhD, (Co-PI) Department of Chemistry, College of Science, Texas A&M University
  • Jon Skare, PhD, (Co-PI) Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center
2. Strategies for Development of a Transgenic Knockout Guinea Pig (2018)

The specific aims of this proposal will seek to develop protocols and reagents for realistic generation of transgenic knockout (KO) animals. This data will provide the corner stone of preliminary data for future NIH R01 proposals that will develop transgenic KO guinea pigs for use in various human disease models. Additionally, preliminary data related to the second aim will also support other GP specific NIH R01 applications. Initial proof of principle CSTR studies will focus on standardization of superovulation and embryo isolation strategies as part of aim one and will utilize an inbred strain 2 GP colony established by the investigators at TAMU. The second aim will develop targeted CRISPR/Cas9 knockout strategies on selected genes in newly established guinea pig fibroblast and trophoblast cell lines to demonstrate the feasibility of applying this knockout technology to the guinea pig.

  • Alistair McGregor, PhD, (PI) Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University
  • Yeon Choi, PhD, (Co-PI) Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University
  • Mark Westhusin, PhD, (Co-PI)Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
  • Charles Long, PhD, (Co-PI)Department of Veterinary Physiology & Pharmacology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
3. Engineering Novel Protein Therapeutics Against Shiga Toxin 1 (2017)

The overall goal of this study is to engineer a series of antibody-like toxin-binding proteins that promote the formation of toxin-immune-complexes against Shiga toxin-producing E. coli (STEC). As a scaffold for the proposed toxin-binding protein, we will use a designed ankyrin repeat protein (DARPin). DARPins represent a versatile class of binding proteins that have been engineered to bind diverse targets with up to picomolar affinity. An important advantage of DARPins over antibodies is their much smaller size (DARPin 18 kDa vs. antibody ~150 kDa), making DARPins more amenable to multivalent interactions with an antigen. In this project, we will first isolate DARPins that bind the pentameric subunit B of Shiga toxin 1 (Stx1) with high affinity (Aim 1). The binding-epitopes of these DARPins on the toxin will be elucidated by cryo-electron microscope (cryo-EM) (Aim 2). A pair of DARPins that bind non-overlapping epitopes on the toxin will be fused to an engineered Fc domain to form DARPin-Fc and their ability to form multivalent DARPin-Fc-toxin complexes will be confirmed (Aim 3). Successful completion of the proposed pilot study will provide important preliminary data to make this proposal more competitive for federal and private funding agencies.

  • Zhilei Chen, PhD,(PI) Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center
  • Junjie Zhang, PhD, (Co-PI) Department of Biochemistry and Biophysics, College of Science, Texas A&M University
  • Vernon Tesh, PhD, (Co-PI)Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center
4. Modulation of LRRK2-dependent Cytokine Production as a Treatment for Parkinson’s Disease (2017)

The goals of this project are to demonstrate a role for the Parkinson’s Disease (PD)-associated kinase LRRK2 in regulating cytokine expression and evaluate how LRRK2-targeted therapeutics may impact the immune response to bacterial infection and/or mitochondrial damage. Because LRRK2 mutations are the number one genetic component of hereditary PD, LRRK2 inhibitors have emerged as a major family of PD therapeutics. However, despite great interest in this molecule, little is known about how LRRK2 mechanistically contributes to neuronal health or how it may impact other aspects of cellular homeostasis. The Watson lab has established that LRRK2 is critical for cytokine production, in particular type I interferon (IFN) expression, in response to both bacterial infection and mitochondrial damage. Type I IFNs are potent multifunctional signaling factors that are critical for promoting the growth of healthy neurons but cause inflammatory damage if overproduced. We hypothesize that PD-associated LRRK2 mutations dysregulate type I IFN levels systemically, contributing to PD pathogenesis. This proposal aims to (1) uncover the precise biochemical contribution of LRRK2 to type I IFN production in response to infection and mitochondrial damage, (2) interrogate how LRRK2-dependent type I IFN shapes the immune cell milieu both in the periphery and in the brains of mice, and (3) understand how existing LRRK2 inhibitors influence these immune outcomes while assessing the risk of LRRK2 inhibition increasing susceptibility to infection. These crucial experiments will inform the influence of the immune response on PD pathogenesis, the utility of LRRK2-focused immunotherapy development, and the identity of immune-related biomarkers for the progression of PD.

  • Robert O. Watson, PhD,(PI) Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center
  • Pingwei Li, PhD, (Co-PI) Department of Biochemistry and Biophysics, College of Science, Texas A&M University
  • Rahul Srinivasan, PhD, (Co-PI)Department of Neuroscience and Experimental Therapeutics Interdisciplinary Program in Neuroscience, College of Medicine, Texas A&M Health Science Center
5. Multi-function Meshes that Prevent Intestinal Anastomotic Leakage and Surgical Adhesions (2016)

The goal of these studies is to provide a novel single-component approach to improve two prevalent and severe complications following gastrointestinal surgical procedures. Specifically, the proposed studies will help establish the efficacy of a clinical treatment to accelerate anastomotic healing and simultaneously provide a temporary barrier to prevent surgical adhesions. Given the prevalence of these procedures as well as the high morbidity and healthcare costs of these complications, the proposed bilayer mesh will have a strong clinical impact. We hypothesize that enhancing anastomotic healing with a gelatin matrix will limit AL and reduce surgical adhesions. Furthermore, we believe that a bioinert hydrogel layer on the gelatin mesh will further reduce surgical adhesions by creating a temporary barrier during the inflammation and remodeling phase of healing. To this end, we have developed a methodology to generate bilayer meshes that combine a gelatin layer to promote healing at the anastomoses and a bioinert and biodegradable hydrogel layer to prevent surgical adhesions. We will evaluate the ability of this bilayer wrap to enhance anastomotic healing and reduce the incidence of surgical adhesions using a rat colon resection and anastomosis model developed in our laboratory.

  • Elizabeth Cosgriff-Hernandez, PhD, Department of Biomedical Engineering, Texas A&M University
  • Noah Cohen, VMD, PhD, Department of Large Animal Clinical Sciences, Texas A&M University
  • Canaan Whitfield, DVM, PhD, Department of Large Animal Clinical Sciences, Texas A&M University
  • Brad Weeks,DVM, PhD, Department of Large Animal Clinical Sciences, Texas A&M University
  • Robert Alaniz, PhD, Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University
6. PRESCIENT: An Integrated System for Predicting Vaccine Efficacy (2016)

A key component of vaccine efficacy is the induction of pathogen-specific antibodies (Abs) with neutralizing activity. In fact, sufficient levels of pre-existing or introduced neutralizing Abs (nAbs) can prevent disease, even when other arms of the immune system are missing or non-responsive. Neutralizing antibodies can also be employed to develop passive Ab therapeutics. Unfortunately, modern approaches for identifying Abs with neutralizing activity are costly, time consuming, and often unsuccessful. The goal of this project is to develop a novel lab-on-a-chip technology for the global determination of the functional repertoire of Abs elicited by diverse vaccine candidates, which will facilitate our ability to design and advance to licensure those that elicit the most favorable responses. This novel technology (PRESCIENT, Platform for the Rapid Evaluation of vaccine SucCess using Integrated Microfluidics ENabled Technology) will feature a powerful droplet microfluidics system that performs unbiased, functional assays of Ab neutralization/enhancement in a high throughput and automated fashion. As such, PRESCIENT will enable identification of the best vaccines before they are advanced for costly and time-consuming clinical evaluation.

  • Arum Han, PhD, Department of Electrical and Computer Engineering, Texas A&M University
  • Julian Leibowitz, PhD, Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University
  • Paul de Figueiredo, PhD, Departments of Plant Pathology & Microbiology; Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences; and Microbial Pathogenesis and Immunology, College of Medicine; Texas A&M University
7. Development of a Novel Preclinical Animal Model and Intervention Strategy for Zika Virus (2016)

The goal of this project is to develop a novel animal model for Zika virus (ZIKV) studies (inbred strain 2 guinea pigs) which is currently utilized by the investigators for their congenital cytomegalovirus (CMV) research. The guinea pig placenta structure is similar to human (unlike the mouse) which makes it a useful model to study congenital infection. An effective, practical and realistic animal model for ZIKV is lacking in the field. Although a transgenic interferon receptor knockout mouse model was recently developed, this provides limited options for evaluation of vaccine strategies. Currently, nonhuman primate models are being explored to study ZIKV. However, such studies are likely to be expensive and pursuit of multiple intervention strategies limited. The proposed research will evaluate ZIKV tropism in newly established guinea pig cell lines and also investigate pathogenicity and preliminary vaccine immune responses in the guinea pig as well as vaccine response in the mouse model. The research will act as supporting data for future NIH proposals related to the development of intervention strategies against congenital ZIKV and pathogenicity of the congenital ZIKV infection. Importantly, NIH has recently placed ZIKV research and in particular development of intervention strategies as a high priority.

  • Alistair McGregor, PhD, Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University
  • Yeon Choi, PhD, Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University
  • Waithaka Mwangi, PhD, Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University
8. Novel Technologies for Multiscale Nanocomposite Scaffolds and Non-invasive Characterization for Bone Regeneration (2015)

This project will further investigate the use of human mesenchymal stem cells (hMSC) for their ability to promote bone healing. We will develop a multiscale hMSC delivery scaffold that provides steady release of the inhibitor GW9662 and of BMP-2 from poly(lactic-co-glycolic acid) spheres containing multi-stage vectors (PLGA-MSVs) integrated into a collagen scaffold. All experiments will be performed with both human and canine MSCs in preparation for preclinical studies in dog models of long bone healing. Microscale spatially-dependent changes in composition and stiffness of the scaffold in vitro and in vivo will be quantified with a novel combined Raman and Brillouin spectroscopy system and correlated with conventional colorimetric staining and micro-CT densitometry measurements.

  • Roland Kaunas, PhD, Department of Biomedical Engineering, Texas A&M University
  • Vlad Yakovlev, PhD, Department of Biomedical Engineering, Texas A&M University
  • Brian Saunders, PhD, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University
  • Ennio Tasciotti, PhD, Department of Nanomedicine, Houston Methodist Research Institute
9. Nanoparticle-mediated Tetrahydrobiopterin Delivery for Attenuation of Cardiovascular Disease (2015)

The overall goal of this project is to develop an effective therapeutic regimen to augment tetrahydrobiopterin (BH4) levels in endothelial cells in order to increase their ability to synthesize nitric oxide, thereby improving vascular function and delaying/attenuating development of subsequent cardiovascular disease (e.g. atherosclerosis). To test our hypothesis that BH4-loaded solid lipid nanoparticles (SLNs), delivered via oral administration, would delay/attenuate the well-characterized atherogenesis noted in an ApoE- and insulin-deficient mice, we propose to 1) determine the optimal treatment schedule for orally administered BH4-loaded SLNs for long-term reversal of endothelial dysfunction in a model of diabetes-associated atherosclerosis, and 2) demonstrate that orally administered BH4-loaded SLNs reduce the risk of atherosclerosis associated with diabetes.

  • Cynthia Meininger, PhD, Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center
  • Anatoliy Gashev, MD, PhD, DMSci, Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center
  • Guoyao Wu, PhD, Department of Animal Science, Texas A&M University
  • John Cooke, MD, PhD, Department of Cardiovascular Sciences, The Methodist Hospital Research Institute
  • Ennio Tasciotti, PhD, Department of Nanomedicine, Houston Methodist Research Institute
  • Cristine Heaps, PhD, Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University
  • George Stoica, DVM, PhD, Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University
  • Katherine Kelly, research specialist, Department of Medical Physiology, College of Medicine, Texas A&M Health Science Center
  • Roberto Molinari, postdoctoral fellow, Department of Nanomedicine, Houston Methodist Research Institute
10. Dietary n-3 Polyunsaturated Fatty Acids Ameliorate Cancer-induced Inflammation by Suppressing Proinflammatory T Cell Activation and Effector Functions (2014)

This research project will investigate two major mechanisms by which dietary n-3 PUFA suppress proinflammatory CD4+ T cell functions in cancer patients. A placebo-controlled, randomized clinical trial of docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3) supplementation in cancer patients will be conducted in order to investigate these two distinct mechanisms of pro- inflammatory CD4+ T cell suppression. The goal is to determine 1) the effect of dietary EPA/DHA supplementation on the clustering/activation of raft-associated signaling proteins at the immunological synapse (IS) in naïve CD4+ T cells from cancer patients, and 2) the effects of dietary EPA/DHA supplementation on the metabolic profile of naïve CD4+ T cells from cancer patients and their propensity to differentiate into pro-inflammatory or anti-inflammatory effector T cell sub-sets

  • Robert S. Chapkin, PhD, Department of Nutrition and Food Science, College of Agriculture and Life Sciences, Texas A&M University
  • Nicolaas E. Deutz, MD, PhD, Department of Health and Kinesiology, College of Education and Human Development, Texas A&M University
  • David N. McMurray, PhD, Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center
  • Xian C. Li, MD, PhD, Immunobiology Research Center & Transplant Immunology Program, Houston Methodist Research Institute
11. Non-antibiotic-based Therapeutics for C. difficile Infection (2014)

The goal of this project is to develop high-potency C. difficile toxin-neutralizing DARPins (designed ankyrin repeat proteins) for anti-CDI therapeutic development in the hopes of alleviating CDI as the leading cause of infectious diarrhea in hospitalized patients. We will 1) use bacteriophage display to isolate DARPins that are able to bind the receptor binding domain of the C. difficile toxin B and apply an anti-toxin function screen in Vero cells to identify toxin-neutralizing DARPins; 2) generate and characterize DARPin-Fc fusions designed to extend the half-life of DARPins in circulation; and 3) investigate the stability of DARPin in gut. The approach of neutralizing bacterial virulence factors with DARPins also offers a new non-antibiotic treatment paradigm for bacterial infection.

  • Zhilei Chen, PhD, Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University Health Science Center
  • Ana Maria Chamoun, postdoctoral research associate, Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University Health Science Center
  • Joseph Sorg, PhD, Department of Biology, Texas A&M University
  • Sally Ward, PhD, Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University Health Science Center
  • Rita Shrestha, graduate student, Department of Biology, Texas A&M University
  • Wei Sun, postdoctoral research associate, Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University Health Science Center
12. Ileal Bacterial Community as a Target for Multiple Sclerosis Treatment (2014)

The goal of this research project is to determine the role of microbiota in the generation of autoreactive T cells by using passive EAE by adoptive transfer of CD4 T cells from wild-type and Nod2-/- mice, and inducing EAE in germ-free mice using a single strain, heat-killed bacteria or bacterial ligand administration. Pyrosequencing and metabolomic analysis, and attenuation of EAE will also be used to determine the mechanisms by which ileal dysbiosis increases the susceptibility to EAE. Another research goal of this project is to determine the role of ileal dysbiosis in a virus-induced model of multiple sclerosis.

  • Koichi Kobayashi, MD, PhD, Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center
  • Jane Welsh, PhD, Department of Veterinary Integrative Biosciences, Texas A&M University
  • Arul Jayaraman, PhD, Department of Chemical Engineering and Biomedical Engineering, Texas A&M University
  • Eamonn M Quigley, MD, Division of Gastroenterology and Hepatology, Houston Methodist Hospital
13. Determination of the Competency of Electronic Health Record Data to Support Outcomes Feedback for Medical Interventions (2014)

This investigation aims to engineer a new knowledge-based system of per encounter outcomes feedback and to train that new system with historical data as a launch point for effective patient-centric outcomes feedback (or to characterize the shortfall and remediation required to advance). Results will be prescriptive for health care data collection, clinical data repositories and health information exchanges that empower outcomes feedback with adequate potency to impact effective delivery of care, reduce cost of improved outcomes and optimize quality of life.

  • Duane Steward, DVM, MSIE, PhD, Center for Biomedical Informatics, Texas A&M Health Science Center
  • Craig Borchardt, PhD, Department of Humanities in Medicine, College of Medicine, Texas A&M Health Science Center
  • James N. Burdine, DrPH, School of Public Health, Texas A&M Health Science Center
  • Nancy Dickey, MD, Departments of Family & Community Medicine and of Medical Humanities, College of Medicine, Texas A&M Health Science Center
  • Sharon Kerwin, DVM, MS, Department of Veterinary Surgery, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University
  • Allen J. Roussel, DVM, MS, Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University
  • Brett Trusko, PhD, MBA, Center for Biomedical Informatics, Texas A&M Health Science Center
  • Stephen Wong, PhD, PE, Department of Radiology; Bioinformatics program, Houston Methodist Research Institute
14. Cannabinoid CB2 Receptor Selective Agonists to Improve Prognosis of Pancreatic Cancer (2013)

The goal of this project is to develop preclinical/clinical candidate of novel chemotherapeutics from CB2 receptor selective agonists for treatment of pancreatic cancer. This research focuses on a novel class of anticancer agents to generate sufficient data to support application of extramural funding to carry drug development towards identification of a clinical candidate and filing of IND application.

  • Dai Lu, PhD, Department of Pharmaceutical Sciences, Rangel College of Pharmacy, Texas A&M Health Science Center
  • Paul Chiao, PhD, Department of Molecular and Cellular Oncology, M.D. Anderson Cancer Center, Houston
  • Alexandros Makriyannis, PhD, Department of Pharmaceutical Sciences, Bouve’ College of Health Sciences, Northeastern University
15.  Manipulation of the Renin-Angiotensin System as Therapy for Viral Pneumonias (2013)

This research employs the MHV-1 mouse model of SARS and the PR8 mouse adapted influenza virus model of severe influenza virus pneumonia to investigate the repurposing of several drugs in widespread use to control hypertension and other cardiovascular disease by blockage of the renin angiotensin system {RAS} to treat viral pnuemonias. This study, if successful in demonstrating that blockade of the RAS ameliorates morbidity, pulmonary pathology, or mortality in either of these mouse models, will serve as the basis of additional grant proposals.

  • Julian Leibowitz, MD, PhD, Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M Health Science Center
  • David Dostal, PhD, Department of Internal Medicine, College of Medicine, Texas A&M Health Science Center
  • Shekhar Ghamande, MD, Department of Internal Medicine, College of Medicine, Texas A&M Health Science Center