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A novel mechanism of action for an actionable predictive biomarker for antitumor therapies

ÌýÌýTodd Pitts (ÃÛÌÇÖ±²¥ Anschutz; Medical Oncology)
ÌýÌýXuedong Liu (ÃÛÌÇÖ±²¥ Boulder; Biochemistry)
​ÌýÌýExisting collaboration ($125,000)

This project will define the mechanism of action of a novel biomarker in modulating the effectiveness of a targeted cancer therapeutic drug.

The team aims to determine whether this new biomarker can be used to identify patients who are most likely to respond to the treatment, which could have important implications for improving cancer treatment outcomes.

Developing a high-throughput and accelerated antibiotic susceptibility testing method

ÌýÌýLakshmi Chauhan (ÃÛÌÇÖ±²¥ Anschutz; Infectious Disease)
ÌýÌýAnushree Chatterjee (ÃÛÌÇÖ±²¥ Boulder; Chemical and Biological Engineering)

This project will assess the potential for the Geometric Viability Assay (GVA) to accelerate antibiotic sensitivity testing (AST) in patients diagnosed with sepsis, and explore antibiotic combinations against multidrug resistant pathogens. GVA is a recently invented, high throughput viability assay which uses common lab consumables to reduce both the time and reagents for AST by over 10-fold.Ìý Key areas of investigation will include the accuracy, scalability, cost, and time savings for the GVA technique over current clinical standards.

The effect of human GCKR P446L genetic variant on alcohol behaviors and metabolism

ÌýÌýDarleen Sandoval (ÃÛÌÇÖ±²¥ Anschutz; Pediatrics)
ÌýÌýKayla Sprenger (ÃÛÌÇÖ±²¥ Boulder; Integrative Physiology)
ÌýÌýNew collaboration ($50,000)

This project will study the functional consequences of a common genetic variant in the glucokinase regulator gene (GCKR) associated with increased risk for alcohol use disorders and metabolic disorders such as type 2 diabetes.

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Mechanisms of zinc-dependent maintenance of heterochromatin domains

ÌýÌýSrinivas Ramachandran (ÃÛÌÇÖ±²¥ Anschutz; Biochemistry & Molecular Genetics)
ÌýÌýAmy Palmer (ÃÛÌÇÖ±²¥ Boulder; Biochemistry)
ÌýÌýNew collaboration ($50,000)

Zinc is an essential micronutrient that is used as a cofactor in over half of human DNA-binding proteins. In this project, we will uncover how zinc can modulate access to our genome by regulating the function of DNA-binding proteins that chelate zinc. This research could reveal a new, previously unexplored mechanism of regulation of gene expression and would have a profound impact for fundamental biology and disease biology.

Multi-generation impact of developmental nicotine exposure on mitochondrial function

ÌýÌýManisha Patel (ÃÛÌÇÖ±²¥ Anschutz; Pharmaceutical Sciences)
ÌýÌýJerry Stitzel (ÃÛÌÇÖ±²¥ Boulder; Integrative Physiology, Institute for Behavioral Genetics)
ÌýÌýNew collaboration ($50,000)

The goal of the project is to determine the effect of nicotine exposure in utero on mitochondrial function in directly exposed offspring and the next generation offspring.

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Novel methods to prospectively predict the occurrence of severe behavior problems in youth

ÌýÌýPatrick Romani (ÃÛÌÇÖ±²¥ Anschutz; Psychiatry)
ÌýÌýSidney D'Mello (ÃÛÌÇÖ±²¥ Boulder; Computer Science, Psychology & Neuroscience; Institute of Cognitive Science)
ÌýÌýNew collaboration ($50,000)

This research will seek to identify relations between the occurrence of severe problem behaviors and changes in physiologic states. The team will identify physiologic signals that predict the occurrence of severe problem behavior at least 60-90 seconds in advance.

Peptide modulators of CaV3.2 for treating pain disorders

ÌýÌýSlobodan Todorovic (ÃÛÌÇÖ±²¥ Anschutz; Anesthesiology and Neuroscience)
ÌýÌýMichael Stowell (ÃÛÌÇÖ±²¥ Boulder; Molecular, Cellular and Developmental Biology)
​ÌýÌýExisting collaboration ($125,000)

Developing peptide modulators of CaV3.2 for treating pain disorders will directly impact pain treatment by directly blocking the source, rather than ameliorating pain through separate pathways whose manipulation may have unintended side effects such as addiction.

Pericentrin self-assembly regulates intracellular trafficking for cilia formation and signaling

ÌýÌýChad Pearson (ÃÛÌÇÖ±²¥ Anschutz; Cell and Developmental Biology)
ÌýÌýLoren Hough (ÃÛÌÇÖ±²¥ Boulder; Physics, BioFrontiers Institute)
​ÌýÌýExisting collaboration ($125,000)

This project will illuminate how precise control of the biophysical properties of pericentrin is coordinated to ensure formation of functional trafficking droplets, elucidating fundamental biological events in intracellular trafficking, cilia formation, and ciliary signaling. These events are defective in DS and have important implications for the manifold of human diseases associated with pericentrin, centrosomeÌýand ciliary defects.

Postural orthostatic tachycardia syndrome in persons with mild traumatic brain injury: vestibular-mediated mechanisms and brain biomarkers

ÌýÌýJeffrey Hebert (ÃÛÌÇÖ±²¥ Anschutz; Physical Medicine and Rehabilitation)
ÌýÌýAllison Anderson (ÃÛÌÇÖ±²¥ Boulder; Aerospace Engineering)
ÌýÌýNew collaboration ($50,000)

This project will elucidate mechanisms and biomarkers of postural orthostatic tachycardia syndrome (POTS) in persons with mild traumatic brain injury, with extension of the findings as a surrogate to the concept of astronauts returning to Earth following physiological deconditioning from long-duration microgravity exposure. The aims of the current pilot study are foundational to the investigative team's long-term objectives of discovering precise treatments for persons with POTS and for astronauts, a major chasm in research and standard of care.

Prefrontal mechanisms underlying the enduring impact of early life adversity

ÌýÌýWon Chan Oh (ÃÛÌÇÖ±²¥ Anschutz; Pharmacology)
ÌýÌýMichael Baratta (ÃÛÌÇÖ±²¥ Boulder; Psychology and Neuroscience)
ÌýÌýNew collaboration ($50,000)

This project will identify the cellular underpinnings that transduce early life adversity into altered prefrontal cortex synaptic activity and behavior in adulthood. We will elucidate and link prefrontal circuit dynamics to its function, encompassing real-time physiological, behavioral, and cognitive outputs. A better understanding of the neurobiological mechanisms that link early life stress to prefrontal cortex impairment will be significant, as it has the potential to guide new strategies for treating anxiety disorders later in life.