Location

Jacksonville, Florida

SUMMARY

Mercedes Prudencio, Ph.D., is interested in deciphering the roles of transactive response DNA-binding protein 43 (TDP-43) and chromosome 9 open reading frame 72 (C9orf72) in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Toward this goal, Dr. Prudencio utilizes a variety of research tools, including animal modeling and several cell and molecular biology techniques.

Dr. Prudencio also studies defects in ribonucleic acid (RNA) — biological molecules that determine what gene information is used to guide protein synthesis. In particular, she aims to identify disease-specific RNA defects that may serve as reliable blood-based biomarkers that will aid in ALS and FTD diagnosis, allowing more efficient assessment of drug efficacy in clinical trials.

Focus areas

  • Molecular mechanisms involving TDP-43, SORT1 and PGRN in FTD. The major protein that makes up the inclusions found in FTLD-U and ALS is TDP-43, a nuclear protein known to be involved in RNA metabolism. Dr. Prudencio's research demonstrated that changes in SORT1 splicing, caused by loss of TDP-43 function in disease, lead to an imbalance in progranulin (PGRN), a growth factor required to maintain neuronal health. Her work focuses on studying the interplay among TDP-43, SORT1 and PGRN, and how the inhibition of SORT1 binding to PGRN may be a viable therapeutic approach to increase PGRN levels in patients with PGRN-deficient FTD.
  • Transcriptome changes in ALS and FTD. A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic abnormality in FTD and ALS. Dr. Prudencio is interested in studying RNA changes derived from the C9orf72 repeat expansion in ALS and FTD. In particular, she uncovered that the transcriptome changes found in diseased C9orf72 repeat expansion and nonexpansion carriers are significantly distinct, suggesting a different mechanism leading to disease. Dr. Prudencio's research is focused on these RNA changes to better understand how different gene mutations lead to the same clinical presentation in ALS with or without FTD comorbidity.
  • Biomarker discovery. Dr. Prudencio is working toward the identification of a panel of transcriptome changes to be used as a biomarker for ALS. Specifically, she wants to evaluate disease-specific defects that can be detected in RNA extracted from blood of symptomatic ALS patients as potential biomarkers of disease.

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 biomarkers in blood would represent a noninvasive and rapid mean for characterizing ALS and FTD patients in order to facilitate screening for clinical trials and potentially support earlier diagnosis.

Blood-based biomarkers linked to disease progression could allow more efficient assessment of drug efficacy in clinical trials than is possible with current clinical outcome measures. Given that no drug or effective biomarker currently exists to delay disease progression or to aid in ALS and FTD diagnosis, research emerging from these studies will greatly impact the field as it has translational implication toward the clinic and patient care.

Professional highlights

  • Recipient, Outstanding International Student Award, University of Florida, 2006-2009
  • Recipient, Bryan W. Robinson Endowment Award, Tallahassee Memorial Healthcare, 2008

PUBLICATIONS

See my publications

PROFESSIONAL DETAILS

Administrative Appointment

  1. Associate Consultant I-Research, MCF Neuroscience

Academic Rank

  1. Assistant Professor of 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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BIO-00054987

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