Matthew J Delano

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Obesity promotes type 2 diabetes (T2D) the 3rd leading cause of death in the United States and accounts for $237 billion healthcare cost. T2D and obesity promote infections that cause sepsis, the leading cause of mortality in the intensive care unit following traumatic injury. Despite advances in supportive care, sepsis mortality remains 25% and escalates over time. Survival from sepsis depends on emergency myelopoiesis of macrophages (MΦ) to clear bacteria and deescalate inflammation. Resolving inflammation requires MΦ polarization from pro-inflammatory M1 to anti-inflammatory MΦ states. The MΦ ability to polarize depends on the intrinsic plasticity inherited from hematopoietic stem and progenitor cells (HSPCs) during emergency myelopoiesis. Our published data in trauma and sepsis in mice and humans demonstrates that obesity and T2D alter HSPC myelopoiesis, inhibit MΦ plasticity and prevent M1Φ polarization to other functional MΦ states. However, the impact of altered MΦ myelopoiesis and restricted M1Φ polarity on sepsis pathogenesis is unknown. A critical need exists to understand the mechanisms by which obesity and T2D alter myelopoiesis, inhibit MΦ plasticity and prevent MΦ polarity to promote bacterial sepsis mortality. We hypothesize that obesity and T2D prime HSPC myelopoiesis to produce dysfunctional M1Φs incapable of bacterial clearance, and effective polarization which hinder inflammation resolution during sepsis and cause mortality. We will test the hypothesis with the following aims that, when completed, will fill the current knowledge void and improve sepsis survival. In Aim 1 we will determine the mechanisms in T2D and obesity that alter myelopoiesis in bacterial sepsis. The findings will reveal how obesity and T2D prime HSPCs and alter myelopoiesis to prevent MΦ polarity in mice and humans with sepsis. In Aim 2 we will identify the functional consequences of obese, T2D M1Φs unable to polarize to other activation states during bacterial sepsis. We will explore how restricted MΦ polarity effects immune cell responses and cytokine production to define how T2D and obesity impede inflammation resolution. The data generated will identify new pathways that promote aberrant myeloid production, restricted MΦ plasticity and prevent inflammation resolution during bacterial sepsis. Novel targeted therapies can then be developed for clinical implementation for bacterial eradication, wound healing and survival from sepsis in obesity and T2D.

Yulia Sevryugina

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Study of Pandemic Publishing: How Scholarly Literature is Affected by COVID-19 Pandemic
This project addresses the quality of recently published COVID-19 publications. With the COVID-19 pandemic, researchers publish a lot their research as preprints. And while preprints are an important development in scholarly publishing, they are works in progress that need further refinement to become a more rigorous final product. Scholarly publishers are also taking initiatives to accelerate publication process, for example, by asking reviewers to curtail requests for additional experiments upon revisions. Sacrificing rigor for haste inevitably increases the likelihood of article correction and retraction, leading to spread of false information within supposedly trustworthy sources that have a peer-reviewing process in place to ensure proper verification. I study the quality of COVID-19 related scholarly works by using CADRE’s datasets to identify signs of incoherency, irreproducibility, and haste.

9.9.2020 MIDAS Faculty Research Pitch Video.

Rudy J. Richardson

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Applications of computational tools for molecular modeling (Discovery Studio, ICM-Pro, MOE, and YASARA) and data science (ADMET Predictor, KNIME, Origin Pro, Prism, Python, and R) to computational toxicology, drug discovery, homology modeling, molecular dynamics, and protein structure/function prediction. Current special interests include therapeutics for neurodegenerative disorders (Alzheimer’s, Parkinson’s, and motor neuron diseases) and infectious diseases (COVID-19).

3D alignment of acetylcholinesterase (AChE) from mouse (magenta) and electric eel (gray) showing the amino acid residues of the catalytic triad.

Robert Ploutz-Snyder

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My work falls into three general application areas. I am an applied (accredited) biostatistician with a strong team science motivation and I collaborate with scientists in primarily the biomedical sciences, contributing expertise in experimental design, statistical analysis/modeling, and data visualization. I have held faculty appointments in Schools of Medicine and Nursing, and also worked as a senior scientist in the Human Research Program at the NASA Johnson Space Center. I currently direct an Applied Biostatistics Laboratory and Data Management Core within the UM School of Nursing, and maintain several collaborative research programs within the School, at NASA, and with collaborators elsewhere.

Kenichi Kuroda

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Synthetic polymers have been used as a molecular platform to develop host-defense antimicrobial peptide (AMP) mimics toward the development of “polymer antibiotics” which are effective in killing drug-resistant bacteria. Our research has been centered on the AMP-mimetic design and chemical optimization strategies as well as the biological and biophysical implications of AMP mimicry by synthetic polymers. The AMP-mimetic polymers showed broad-spectrum activity, rapid bactericidal activity, and low propensity for resistance development in bacteria, which represent the hallmarks of AMPs. The polymers form amphipathic conformations capable of membrane disruption upon binding to bacterial membrane, which recapitulates the folding of alpha-helical AMPs. We propose a new perception that AMP-mimetic polymers are an inherently bioactive platform as whole molecules, which mimic more than the side chain functionalities of AMPs. The chemical and structural diversity of polymers will expand the possibilities for new antimicrobial materials including macromolecules and molecular assemblies with tailored activity. This type of synthetic polymers is cost-effective, suitable for large-scale production, and tunable for diverse applications, providing great potential for the development of versatile platforms that can be used as direct therapeutics or attached on surfaces.

Xudong (Sherman) Fan

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We conduct research to analyze breath from patients in order to diagnose and monitor diseases.
We also develop imaging modalities to analyze tissues for cancer diagnosis

Hernán López-Fernández

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I am interested in the evolutionary processes that originate “mega-diverse” biotic assemblages and the role of ecology in shaping the evolution of diversity. My program studies the evolution of Neotropical freshwater fishes, the most diverse freshwater fish fauna on earth, with an estimate exceeding 7,000 species. My lab combines molecular phylogenetics and phylogeny-based comparative methods to integrate ecology, functional morphology, life histories and geography into analyses of macroevolutionary patterns of freshwater fish diversification. We are also comparing patterns of diversification across major Neotropical fish clades. Relying on fieldwork and natural history collections, we use methods that span

Jonathan Terhorst

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I develop probabilistic and statistical models to analyze genetic and genomic data. We use these methods to study evolution, natural selection, and human history. Recently, I have been interested in applying these techniques to study viral epidemics (e.g., HIV) and cancer.

Estimates of recent effective population sizes for various human subpopulations.