Location

Jacksonville, Florida

Contact

Prudencio.Mercedes@mayo.edu

SUMMARY

Proteinaceous inclusions of TAR DNA-binding protein 43 (TDP-43) are hallmark pathological features in most patients with amyotrophic lateral sclerosis (ALS), about half of all patients with frontotemporal dementia (FTD) and over 60% of patients with Alzheimer's disease (AD). Further, TDP-43 inclusions have also been found in more rare neuromuscular disorders such as spinocerebellar ataxia 3 (SCA3).

The RNA Metabolism in Neurodegenerative Disease Laboratory at Mayo Clinic, led by Mercedes Prudencio, Ph.D., is focused on understanding disease mechanisms to identify novel biomarkers and therapeutic targets for diseases characterized with TDP-43 pathology (TDP-43 proteinopathies). Toward this goal, Dr. Prudencio utilizes a variety of research tools, including human biospecimens, animal modeling, and several cell and molecular biology techniques.

Focus areas

  • Evaluating the role of TDP-43 RNA targets in disease. TDP-43 regulates many facets of RNA metabolism; thus, TDP-43 loss-of-function in disease results in the accumulation of aberrant transcripts. One of these transcripts may be the recently discovered variant of a protein involved in axonal regeneration: stathmin-2 (STMN2). The accumulation of a truncated variant of STMN2 (tSTMN2), with a concurrent decrease in the full-length STMN2 transcript has been shown in ALS, resulting from TDP-43 loss-of-function.

    Dr. Prudencio and her colleagues have found that increased levels of tSTMN2 RNA associate with TDP-43 pathology and with an earlier age of FTD/ALS onset. These findings not only suggest tSTMN2 could be used as a biomarker for TDP-43 pathology in FTD/ALS, but also, the fact that TDP-43 dysfunction is also associated with AD is quite intriguing and increases the importance of evaluating splicing changes of stathmin-2 in AD cases associated with TDP-43 dysfunction. In addition to STMN2, Dr. Prudencio's laboratory aims to follow up novel TDP-43-mediated splicing events specific to AD or FTD/ALS, to understand their regulation, their role in the pathobiology of AD or FTD/ALS, and to explore their biomarker potential.

  • Biomarker discovery. Dr. Prudencio currently co-leads the Neurological Disease Biorepository and Biomarker Initiative at Mayo Clinic's campus in Jacksonville, Florida. In doing so, she collaborates in several biomarker projects. In particular, she is interested in following her biomarker studies in SCA3 as well as identifying disease pathways that may lead to the identification of novel therapeutic targets.

    Further, she collaborates in other exciting biomarker studies, such as the use of neurofilament light, a biomarker of neuronal injury that is elevated in patients with COVID-19, and which levels associate with worse clinical outcomes. Since a large proportion of hospitalized patients with COVID-19 report neurological symptoms, she is investigating whether neurofilament light levels during infection could help investigators understand the potential long-term neurological consequences of individuals who overcome COVID-19.

Significance to patient care

A better understanding of disease mechanisms will allow the development of animal models to study human disease, and the utilization of these models for development of new and more effective therapies to fight disease. In addition, identification of disease biomarkers is key to facilitate screening for clinical trials, potentially support earlier diagnosis, as well as allow more efficient assessment of drug efficacy in clinical trials than is possible with current clinical outcome measures. Thus, research emerging from these studies will greatly impact the field as it has translational implication toward the clinic and patient care.

Professional highlights

  • Women in Science Travel Fund, The Rockefeller University, 2020
  • Travel Award, American Neurological Association, 2019
  • Outstanding International Student Award, University of Florida, 2006-2009
  • Bryan W. Robinson Endowment Award, Tallahassee Memorial Healthcare, 2008

PROFESSIONAL DETAILS

Administrative Appointment

  1. Associate Consultant II-Research, MCF Neuroscience

EDUCATION

  1. Research Associate - Neuroscience Mayo Clinic in Florida
  2. Postdoctoral Training - Neuroscience Mayo Clinic in Florida
  3. Ph.D. University of Florida Medical School, University of Florida
  4. BSc - Biology Universidad de Extremadura
  5. Undergraduate Research Assistant University of Florida
  6. Undergraduate Research Assistant Ohio State University
  7. Undergraduate Research Assistant Washington State University
  8. Diploma - English Language Escuela Oficial de Idiomas
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