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Acute intermittent hypoxia in persons with spinal cord injury: studying corticospinal drive and motor adaptation

ÌýÌýAndrew Smith (ÃÛÌÇÖ±²¥ Anschutz; Department of Physical Medicine and Rehabilitation, Physical Therapy Program, School of Medicine)
ÌýÌýAndrew Q Tan (ÃÛÌÇÖ±²¥ Boulder; Department of Integrative Physiology, ÃÛÌÇÖ±²¥ Boulder Center for Neuroscience)
ÌýÌýNew collaboration ($50,000)

Spinal cord injury (SCI) disrupts sensory and motor pathways, resulting in lifelong mobility impairments and loss of functional independence. This proposal will characterize how breathing modest bouts of low oxygen (acute intermittent hypoxia; AIH) may enhance the excitability of spared pathways to the lower limb as well as augment motor adaptation in humans with SCI.

Biomaterial and small molecule targeting of macrophage BRD4 to prevent pathological cardiac fibrosis

ÌýÌýTimothy McKinsey (ÃÛÌÇÖ±²¥ Anschutz; Division of Cardiology, School of Medicine)
ÌýÌýKristi Anseth (ÃÛÌÇÖ±²¥ Boulder; Department of Chemical and Biological Engineering and BioFrontiers Institute)
​ÌýÌýExisting collaboration ($125,000)

We aim to uncover novel mechanistic information about the pathological role of inflammatory cells on cells in the heart and the progression of cardiac fibrosis. Specifically, we will study how macrophages control fibroblast activity through cellular, biomechanical and epigenetic cues with the goal of identifying new therapeutic innovations for patients suffering from end-stage cardiac and valvular fibrotic diseases.

Cell-type, pathwayÌýand neurotransmitter-specific regulation of feeding circuitry

ÌýÌýChristopher Ford (Pharmacology), ÃÛÌÇÖ±²¥ Anschutz
ÌýÌýDavid Root (Psychology and Neuroscience), ÃÛÌÇÖ±²¥ Boulder
ÌýÌýNew collaboration (up to $50,000)

Eating-related disorders have high mortality rates and limited treatment options. In an effort to identify new neuronal targets against eating-related disorders, we will identify how stress and feeding neuronal circuits interact as well as identify if modifying these circuits reduces stress-induced anorectic behavior in mice.

Chronic inflammation and ECM degeneration as key mediators of pelvic organ prolapse

ÌýÌýKathleen Connell (ÃÛÌÇÖ±²¥ Anschutz; Obstetrics & Gynecology, School of Medicine)
ÌýÌýVirginia Ferguson (ÃÛÌÇÖ±²¥ Boulder; Department of Mechanical Engineering, College of Engineering and Applied Sciences)
ÌýÌýNew collaboration ($50,000)

Pelvic organ prolapse is a costly, and debilitating disorder that impacts millions of women, yet the underlying mechanisms responsible for the compromise of the pelvic support tissues are poorly understood and few animal models to study prolapse exist. We have identified evidence of inflammation and metabolic endotoxemia (ME) in pelvic support tissues from women with prolapse, and our studies in this proposal will establish an ME mouse model that will define the impact of circulating lipopolysaccharide on inflammation, extracellular matrix content and biomechanical properties of critical pelvic support structures in order to create a practical animal model to further study the effects of ME on the pelvic floor, and ultimately develop early intervention strategies to prevent pelvic organ prolapse.

Combining innovative engineered in vitro and in vivo models to determine the role of myeloid derived suppressor cells in sepsis

ÌýÌýRichard Tobin (Medicine, Surgical Oncology), ÃÛÌÇÖ±²¥ Anschutz
ÌýÌýLaurel Hind (Chemical and Biological Engineering), ÃÛÌÇÖ±²¥ Boulder
ÌýÌýNew collaboration (up to $50,000)

This overarching goal of this project is to understand how myeloid derived suppressor cells, a rare immunosuppressive cell population, function during infection to determine if they are a viable target for treating sepsis. Findings from this study could create new therapeutic avenues for the treatment of sepsis and other hard-to-treat infections.

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Combining simulations and experiments to determine protein/ligand-mediated microglial activation in Alzheimer's Disease

ÌýÌýKimberley Bruce (ÃÛÌÇÖ±²¥ Anschutz; Division of Endocrinology, Metabolism and Diabetes, School of Medicine)
ÌýÌýKayla Sprenger (ÃÛÌÇÖ±²¥ Boulder; Chemical and Biological Engineering Department)
ÌýÌýNew collaboration ($50,000)

This study aims to use a novel computational and experimental platform to unravel the molecular complexity of microglial activation, and to identify microglial phenotypes that may protect against Alzheimer's disease development and progression.

Integrated COVID genomic sampling, sequencingÌýand variant tracking

ÌýÌýDavid Pollock (ÃÛÌÇÖ±²¥ Anschutz; Department of Biochemistry and Molecular Genetics, School of Medicine)
ÌýÌýRyan Layer (ÃÛÌÇÖ±²¥ Boulder; BioFrontiers Institute, Computer Science Department)
ÌýÌýNew collaboration ($50,000)

The project aims to follow and assess risk variation associated with evolutionary change in genomic variants of SARS-CoV-2, the virus responsible for COVID-19 in humans. To do this, we will deploy fast and integrated Bayesian sequence and phylogenetic network analysis.

Engineered nanophages for enhanced mucosal delivery

ÌýÌýUday Kompella (Pharmaceutical Sciences), PhD, ÃÛÌÇÖ±²¥ Anschutz
ÌýÌýLoren Hough, PhD, (Physics), ÃÛÌÇÖ±²¥ Boulder
ÌýÌýNew collaboration (up to $50,000)

Since noninvasive mucosal delivery of macromolecules is a major challenge, this project will advance engineered nanophages to overcome the mucosal epithelial barriers. The proof-of-concept will be established using eye drop based ocular delivery of a macromolecule.

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Evaluation of the composition and health risks of environmental micro- and nano-plastics

ÌýÌýSuzhao Li (Medicine, Infectious Disease) ÃÛÌÇÖ±²¥ Anschutz
ÌýÌýWei Zhang (Chemistry), ÃÛÌÇÖ±²¥ Boulder
ÌýÌýNew collaboration (up to $50,000)

This project will help identify the chemical compositions of micro and nanoplastic particles (MNPLs) in water sources and their impacts on human health. The knowledge gained from this study will facilitate our assessment of potential environmental risks caused by MNPLs and provide guidelines on the plastic waste management, water treatment and environment protection system.

Mechanical forces in breast cancer bone metastasis

ÌýÌýPhilip Owens (Pathology), ÃÛÌÇÖ±²¥ Anschutz
ÌýÌýMaureen Lynch (Mechanical Engineering), ÃÛÌÇÖ±²¥ Boulder
​ÌýÌýExisting collaboration (up to $125,000)

The objective of this proposal is to test the hypothesis that osteocytes, the principal mechanosensory cells in bone, control whether physical forces on the skeleton result in a bone-strengthening/tumor suppressive remodeling program or a wound-healing/tumor promoting remodeling program.

Molecular targeting phase-change ultrasound contrast agents for early diagnosis and guided treatment of Type 1 diabetes

ÌýÌýRichard KP Benninger (ÃÛÌÇÖ±²¥ Anschutz; Department of Bioengineering and Department of Pediatrics)
ÌýÌýMark A Borden (ÃÛÌÇÖ±²¥ Boulder; Department of Mechanical Engineering)
​ÌýÌýExisting collaboration ($125,000)

Type1 diabetes follows the immune-mediated destruction of insulin-producing beta cells, requiring life-long insulin therapy and increasing the risk of diabetic complications. We will develop novel molecularly-targeted phase-change ultrasound contrast agents to track the progression of insulitis and guide therapeutic treatments to prevent type 1 diabetes.

Predicting the environmental distributions and pathogenicity of nontuberculous mycobacteria, an emerging group of bacterial pathogens

ÌýÌýMichael Strong (ÃÛÌÇÖ±²¥ Anschutz; Division of Infectious Diseases, School of Medicine, and National Jewish Health)
ÌýÌýNoah Fierer (ÃÛÌÇÖ±²¥ Boulder; Department of Ecology and Evolutionary Biology, Cooperative Institute for Research in Environmental Sciences)
ÌýÌýNew collaboration ($50,000)

Nontuberculous mycobacteria (NTMs) are a diverse group of bacteria with some members of this group capable of causing environmentally acquired pulmonary disease, an emerging public health problem in the U.S. We seek to understand why NTMs vary in their pathogenicity and which particular environments are most likely to harbor pathogenic NTMs.

Swimming through mucus: Anisotropy and other obstacles for bacteria

ÌýÌýChristopher M Evans (ÃÛÌÇÖ±²¥ Anschutz; Division of Pulmonary Sciences and Critical Care Medicine)
ÌýÌýNuris Figueroa (ÃÛÌÇÖ±²¥ Boulder; Department of Physics, College of Arts and Sciences)
ÌýÌýNew collaboration ($50,000)

This study focuses on physical properties of mouse colonic mucus that control bacterial trajectories, and how mucus composition determines those properties. It has to potential to identify causes for chronic penetration of commensal bacteria through mucus in the digestive tract, which is relevant in diseases characterized by changes in the intestinal microbiome, and could lead to new avenues for treatments that will target mechanical properties of mucus.

Understanding AKT1 function regulating interneuronal activity involved in E/I balance

ÌýÌýMolly Huntsman (Pharmaceutical Sciences), ÃÛÌÇÖ±²¥ Anschutz
ÌýÌýCharles Hoeffer (Integrative Physiology), ÃÛÌÇÖ±²¥ Boulder
​ÌýÌýExisting collaboration (up to $125,000)

Our work will provide information about how one kind of cell in the brain, the interneuron, functions in the context of AKT1 mutation, a gene linked to neurological disorders. These studies will facilitate potential therapeutic avenues by determining if approved drugs for other diseases can be used for psychiatric treatment.

Universal autism screening program in audiology clinics

ÌýÌýDeborah Mood (Pediatrics), ÃÛÌÇÖ±²¥ Anschutz
ÌýÌýAngela Bonino (Speech, Language, and Hearing Sciences), ÃÛÌÇÖ±²¥ Boulder
ÌýÌýNew collaboration (up to $50,000)

This project brings together interdisciplinary experts from audiology, developmental psychology, and statistics to reduce the delay in the diagnosis of autism spectrum disorder through the development of a screening program in audiology clinics.