Pilot Award Program
SAC Incubator projects will foster the establishment of extramurally-funded, nationally-recognized centers of excellence in biomedical research with the potential to generate new strategic directions for the School of Medicine and Dentistry and the University. Funded projects will be innovative, multi-investigator, multidisciplinary research projects with the potential to give new life to the overall scientific portfolio of the UR and keep the institution in the forefront of today's fast-paced and competitive scientific landscape. Each SAC Incubator proposal must involve a team of 2 or more co-principal investigators. A multi-PI leadership plan is required.
Prior SAC Incubator Awards
Funded Incubator Project (awarded 7/1/2014):
Project Title: “Intra-tissue refractive index shaping (IRIS) for customizing refractive correction.”
PIs: Krystel Huxlin, Wayne Knox, and Jonathan Ellis.
IRIS is a revolutionary approach to vision correction, which uses a femtosecond laser below the damage threshold of the corneal matrix or hydrogel lenses to alter their refractive index. We have made substantial progress on the proposed aims (summarized below), both in terms of technology development, and demonstrating safety, efficacy and long-term resilience of IRIS in the cat cornea. We are now poised to begin testing in human tissue this summer. Live human experiments/testing are being planned to begin 12 months from now. Regulatory consultants have been engaged and we have begun conversion to GLP and GCP systems in preparation for FDA submission.
Funded Incubator Project (awarded 7/1/2015) :
Project Title: “Novel approaches to overcome therapy resistance in prostate cancer"
PIs: C. Chang, J. Krolewski
Other key personnel: Y. Chen*, C. Fung, E. Guancial, O. Hyrien, F. Li, E. Messing, K. Nastiuk, D. Sahasrabudhe, Y. Sun, R. Wood, S. Yeh*
The long-term goal is to build a research program (P01) focused on developing novel treatments for therapy resistant forms of human prostate cancer (PrCa). The program leverages the discovery – in the Chang lab –of ASC-J9, a curcumin derivative that degrades the androgen receptor (AR). ASC-J9 is particularly valuable because it can circumvent resistance to androgen deprivation therapy (ADT) as well as newer anti-androgen therapies. Individual projects extend the utility of ASC-J9 by investigating the mechanism and pre-clinical efficacy of combining this AR-targeting agent with non-AR therapies (radio-, cytokine directed- and chemotherapy) to treat therapy resistant PrCa.
Funded Incubator Projects (awarded 7/1/2017) :
Imaging and manipulating stem cell division in vivo
PIs: B. Biteau, D. Bergstrahl, P. Oakes
In this proposal, we describe an interdisciplinary research program that capitalizes on live-cell imaging and genetic expertise in our research groups, across three departments and two UofR schools. We will use the Drosophila adult intestine as the model system to address fundamental questions about the maintenance of epithelia by resident stem cells, as it represents an ideal tissue to study oriented stem cell division, cell intercalation and tissue mechanical properties in a genetically tractable model. Work from our laboratories has significantly contributed to the effort of uncovering the mechanisms controlling stem cell self-renewal, spindle orientation or daughter cell placement in epithelia and manipulating mechanical forces at the single cell level. The proposed project aims at establishing novel imaging and optogenetics methods to characterize and manipulate stem cell division orientation and mechanical forces in the fly intestine.
Removing Disparities in Interpersonal Violence Case Processing
PIs: C. Cerulli, A. Berger
Other key personnel: J. Cullen, J. Zavislan
This two phase project is a community-based participatory research (CBPR) study: Phase I involves the review of victim bruising evidence, and Phase II involves leveraging light technology to enhance bruising documentation for victims with darker skin pigmentation. Our team has the requisite skills and leadership to see this project through completion – which includes future R01 applications to improve the health of individuals affected by intimate partner violence (IPV).
Funded Incubator Project (awarded 7/1/2018) :
Biomarkers, mechanisms and interventions for severity of infant RSV infection.
Co-Investigators: T. Mariani, E. Walsh, X. Qiu
Respiratory Syncytial Virus (RSV) infects ~70% of newborn infants annually, with ~100,000 US hospitalizations and ~3 million worldwide, and ~199,000 deaths in underdeveloped countries. We lack biomarkers capable of identifying the likelihood of severe responses to infection in infants without known risk factors, such as prematurity or overt immune deficiencies. We also lack understanding of host biological mechanisms determining the severity of clinical responses in normal, healthy infants. We hypothesize that unique host responses, modified by environmental factors including the airway microbiota, drive disease severity. We are completing three focused, integrated projects, which will facilitate development of multiple grant applications, with the goal of generating sufficient data and enthusiasm to combine them into a program application. Since the initiation of this funding, the core group of investigators, including PIs and co-Investigators, have met monthly (1-1.5 hrs) to review progress and develop plans. In addition, the PIs meet every 2 weeks for 1.5 hours to review data and develop/modify manuscripts. These frequent meetings have facilitated an ongoing level of high productivity for the group, as outlined below.
Funded Incubator Project (awarded 7/1/2019) :
Role of hyperactive neutrophils in the microcirculatory dysfunction of sepsis
Co-investigators: A. Pietropaoli, M. Kim
Sepsis is defined as by a maladaptive host response to infection that causes acute organ dysfunction. This acute organ dysfunction is driven in large part by microvascular dysfunction resulting from the maladaptive host response. Sepsis syndrome is deadly, expensive, and difficult to diagnose, and treatment remains largely supportive and rudimentary. We have recently made two important discoveries that, together, could have substantial impact on both the clinical management of sepsis and the understanding of sepsis pathophysiology: 1) a subset of neutrophils expressing the integrin molecule VLA-3 are maladaptive, associated with sepsis and sepsis outcomes in humans, and mediate microcirculatory dysfunction and organ failure in animal models; 2) a simple and practical ultrasound technique measuring brachial artery reactive hyperemia reflects microvascular function and is strongly and independently predictive of sepsis and sepsis mortality. In this translational research proposal, we will capitalize on our long-standing cross-disciplinary collaboration to determine relationships between neutrophil expression VLA-3 expression, microvascular function, and outcomes in critically ill patients with sepsis. We will further test the extent to which neutrophil expression of VLA-3 mediates microvascular leak in vitro using a novel cell-substrate impedance sensing assay and neutrophils from septic patients. Finally, we will perform RNA transcriptional analysis of these human neutrophils to determine whether transcription profiles differ from neutrophils categorized by high vs low VLA-3 expression, and then focus on these differences to better understand the specific mechanisms by which these maladaptive VLA-3high neutrophils induce vascular barrier dysfunction.
Importantly, this pilot incubator program will also serve as a catalyst to drive further cross-disciplinary and translational sepsis research involving other departments including investigators from departments of Biomedical Engineering, Pediatrics other research centers including Cardiovascular Disease, Infection and Immunity, Lung Biology, and Neuro-medicine and fuel our plans for several multi-PI NIH proposals.