Biology subjects

Vazquez-Hidalgo, E.

Publications and source records attributed to Vazquez-Hidalgo, E..

3 recordsLinked to original sources

bioRxiv2026

PREP-aring is worth it: Success of the Case Western Reserve University Post-baccalaureate Research Education Program and its Scholars

The Post-baccalaureate Research Education Program (PREP), established by the National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health in 2000, was a research-intense, one-year training program for recent college graduates from backgrounds uncommon in science who intended to matriculate with a PhD or MD/PhD program in preparation for an eventual career in biomedical research. Case Western Reserve University had an NIGMS-supported PREP (CasePREP) from 2007 to 2025, the year NIGMS terminated the PREP funding mechanism. A major goal of CasePREP was to prepare post-baccalaureate trainees (termed Scholars) for graduate school, and major metrics of success were measured as Scholars who a) matriculated in and b) completed PhD or MD/PhD programs. A major goal of NIGMS-supported PREPs was the retention of these scientists in the biomedical research workforce. We report here the extent that CasePREP met program goals as well as the economic and scientific impact NIGMS-supported PREP has had for a variety of stakeholders. Data from 18 CasePREP cohorts included self-reported (surveys, interviews, questionnaires) and public data (websites, PubMed, NIH Reporter). Descriptive statistics and large language models were used to describe the major outcomes related to program goals and a new resilience course as well as Scholar productivity and contribution to science. Between 2007 and 2025, CasePREP was awarded $5.6 million USD and trained 108 Scholars. Most (89%) Scholars resided outside of Ohio prior to the start of CasePREP, with 38.89% from Puerto Rico. Almost all (98%) Scholars completed the one-year program in Cleveland, Ohio, and of those, 83% entered a PhD or MD/PhD program. As of September 2025, 46 Scholars have completed a PhD program, two Scholars have completed an MD/PhD program, and 27 are still in training. The attrition rate for CasePREP Scholars in graduate school is currently 14.77%, much lower than the attrition rates of national PhD programs. Most CasePREP Scholars (69.44%) are co-authors on one or more published manuscripts, and these 406 published works have garnered 14,261 total citations, with an average 35.04 citations per publication. Termination of PREP represents a five-year loss of [~]$2.7 million USD to CasePREP, a budget that would have trained an additional 30 Scholars. CasePREP was a great success as measured by its major outcomes. CasePREP Scholars have persisted in science and have made substantial contributions to the scientific workforce and enterprise. PREPs in general provided a crucial bridge for research talents who had little prior research opportunities to realize their potential and career goals. NIGMS termination of PREP support has negative economic consequences and endangers an important pathway to a career in science for Americans who would not otherwise have similar opportunities.

scientific communication and education↗

bioRxiv2021

Downregulation of RyR and NCX in the neonatal rat ventricular myocyte modulates cytosolic

Calcium (Ca2+) is necessary for cardiac muscle contraction. RyR, NCX, and SERCA are key regulatory protein channels for cytosolic Ca2+ in cardiac myocytes. Expression levels of these proteins are a function of development, with protein expression shifting toward the adult phenotype over time. We investigated how downregulation by siRNAs of RyR and NCX affected expression levels of complimentary proteins and the corresponding intracellular Ca2+ transients. We compared experimentally observed Ca2+ transients to those predicted by mathematical models. Experiments show RyR downregulation decreased SERCA and increased NCX protein levels. The associated Ca2+ transient had a decreased amplitude, increased time-to-peak, 50%, and 90% Ca2+ removal with respect to the control cell. NCX downregulation increased SERCA production without significant changes in RyR expression levels. The corresponding [Ca2+] transient had increased amplitude, no change in time-to-peak and 50% Ca2+ removal, and increased 90% Ca2+ removal with respect to the control cell. Computational models that accurately predict the observed experimental data suggest compensatory changes occurring in the expression levels as well as biochemical activity of the regulatory proteins.

cell biology↗

bioRxiv2019

β-adrenergic signaling modulates cancer cell mechanotype through a RhoA-ROCK-myosin II axis

The ability of cells to deform and generate forces are key mechanical properties that are implicated in metastasis. While various soluble and mechanical cues are known to regulate cancer cell mechanical phenotype or mechanotype, our knowledge of how cells translate external signals into changes in mechanotype is still emerging. We previously discovered that activation of {beta}-adrenergic signaling, which results from soluble stress hormone cues, causes cancer cells to be stiffer or less deformable; this stiffer mechanotype was associated with increased cell motility and invasion. Here, we characterize how {beta}-adrenergic activation is translated into changes in cellular mechanotype by identifying molecular mediators that regulate key components of mechanotype including cellular deformability, traction forces, and non-muscle myosin II (NMII) activity. Using a micropillar assay and computational modelling, we determine that {beta}AR activation increases cellular force generation by increasing the number of actin-myosin binding events; this mechanism is distinct from how cells increase force production in response to matrix stiffness, suggesting that cells regulate their mechanotype using a complementary mechanism in response to stress hormone cues. To identify the molecules that modulate cellular mechanotype with {beta}AR activation, we use a high throughput filtration platform to screen the effects of pharmacologic and genetic perturbations on {beta}AR regulation of whole cell deformability. Our results indicate that {beta}AR activation decreases cancer cell deformability and increases invasion by signaling through RhoA, ROCK, and NMII. Our findings establish {beta}AR-RhoA-ROCK-NMII as a primary signaling axis that mediates cancer cell mechanotype, which provides a foundation for future interventions to stop metastasis.

cancer biology↗