Thirty-six Brown researchers, including three from the School of Engineering, are receiving University research awards through 18 Research Seed grants, totaling $1M. Research Seed Funding awards are competitively awarded by the Office of the Vice President for Research and help faculty more successfully advance competitive research proposals by supporting the generation of preliminary data, pursuing new directions or collaborations in research, and other endeavors. Competitive proposals for sizable projects are expected to be submitted to an external funding organization within a year of the completion of the Research Seed Fund period.
Projects from the School of Engineering include: Fabiola Munarin, who is investigating “Immunomodulatory Biomaterials for Treating Ischemia in Diabetic Models”; Tayhas Palmore, who is partnering with Vesna Mitrovic and Edward Walsh to investigate “Reverse Engineering the Synaptic Cleft - the Search for Quantum Information Processing in the Brain”; and Vikas Srivastava, who is researching “Responsive Hydrogel Based pH Regulation of Cancer Tumor Microenvironment to Reduce Metastasis.”
Summaries of the engineering projects are as follows:
Immunomodulatory Biomaterials for Treating Ischemia in Diabetic Models
Ischemic wounds occur when blood flow is reduced in a specific body area, leading to cell death and tissue damage. In diabetes, microvascular complications and unbalanced activation of the immune cells markedly compromise the repair from ischemic wounds, causing slower healing, development of chronic wounds and increased risk for infections.The overall objective of this proposal is to explore the mechanisms of wound healing in diabetes, by signaling of anti-inflammatory cytokines (CSF-1, IL4 and IL-13) via the JAK-STAT pathway, and to develop a novel treatment using preclinical models of non-healing diabetic ulcers. My preliminary data show that CSF-1, IL-4, and IL-13 regulate immune cells polarization and ischemic wound healing in monocyte cultures and non-diabetic animal models. With this proposal, we will elucidate the cytokines-driven regulation of the JAK-STAT signaling cascade in diabetes (Aim 1), we will deliver CSF-1, IL-4 and IL-13 from biomaterials to modulate the plasticity of monocytes isolated from the blood of diabetic rats and humans (Aim 2), and we will examine the healing of ischemic wounds in diabetic rats (Aim 3). This work will advance Brown’s position in the fields of immune engineering and wound healing therapy, will allow the PI to lay a solid foundation for expanding her research program in diabetes, and will be instrumental for attracting external funds. If successful, this project will identify suitable therapeutic targets for treating chronic wounds in diabetic patients, and will accelerate the translation to the clinic of novel immunomodulatory treatments for a patient population in great need.
PI: Fabiola Munarin, Assistant Professor of Engineering (Research)
Reverse Engineering the Synaptic Cleft - the Search for Quantum Information Processing in the Brain
The interdisciplinary team proposes to test the idea that the fundamental principle of a complex brain operation is quantum processing involving nuclear spins of phosphorus as a neural qubit. This idea originates from a reputable theoretical physicist M. Fisher, UCSB. He identified the hypothetical Posner molecule as one that can protect neural qubits very long times and thereby serve as a working quantum-memory. Our novel approach involves harnessing the properties of nuclear spins to study quantum information processing (QIS) in the brain by reverse engineering specific polymers and biomolecules to provide sufficiently long coherence times required for quantum processing. This is orthogonal to the UCSB’s approach that focuses on the search of Posner molecule. The team members are highly complementary and have a well-established prior record of collaborations. Palmore will synthesize polymer based biomaterials with appropriate nuclear spin species, while Mitrovic and Walsh will use the nuclear magnetic resonance (NMR) technique to test possible coherence propagation and test whether such bio-materials can be used as a quantum register to process information. The team has identified the appropriate synthesis and patterning of phosphates into specific isotopically labeled and DNA nanostructure. They have also designed the NMR experiment to test the quantum nature of neural signal transmission, and NMR experiments to test nuclear spin coherence. Our long-term goal is to identify essential biomaterial properties required for QIS and quantum signal transmission using nuclear spins of phosphorus. The ultimate goal is synthesis of artificial neural synapses and memory registers.
PI: Vesna Mitrovic, Professor of Physics
Co-PIs: Tayhas Palmore, Elaine I. Savage Professor of Engineering, Professor of Chemistry; Edward Walsh, Assistant Professor of Neuroscience (Research)
Responsive Hydrogel Based pH Regulation of Cancer Tumor Microenvironment to Reduce Metastasis
Cancer cells are known to create acidic extracellular environments through the excretion of acid byproducts due to irregular metabolic pathways. This unusually acidic extracellular tumor microenvironment compared to healthy tissues may be targeted through cancer therapies. Counteracting the pH of the tumor microenvironment in in vivo mouse models by ubiquitous bicarbonate delivery has shown promise. Currently, an effective method of locally regulating the pH of the tumor microenvironment to reduce cancer progression due to acidosis does is lacking and our research aims to fill this important need by developing a responsive hydrogel pH regulating system by demonstrating its efficacy in cancer treatment. We aim to develop a novel biocompatible pH regulating hydrogel that reduces cancer metastasis and invasion by continuously counteracting the acidosis of the extracellular space. We will conduct in vitro experiments to test proliferation, motility, and invasion of MDA-MB-231 breast cancer cells when exposed to our novel hydrogel. Completion of our study will allow further research into targeted delivery of pH regulating hydrogels in vivo as well as new studies of subcellular cancer cell mechanisms that can be regulated through pH control.
PI: Vikas Srivistava, Assistant Professor of Engineering