# Abnormal Mitochondrial Bioenergetic and Motility Signatures in Human Blood Cells as Indices of Acute Poisoning in Patients

> **NIH NIH K08** · UNIVERSITY OF PENNSYLVANIA · 2021 · $168,696

## Abstract

Project Summary
Poison-related incidents account for over 450,000 hospitalizations and 750,000 emergency department (ED)
visits, with the yearly cost for ED visits exceeding $550 million. It is conservatively estimated that 5,000 deaths
per year and 20,000 injuries in the US are due to mitochondrial poisons (e.g., carbon monoxide (CO), cyanide
(CN), hydrogen sulfide (H2S), phosphides) resulting in mitochondrial inhibition leading directly to cardiac arrest
and/or shock. Exposure to mitochondrial inhibitors occurs in a variety of settings, including fires, occupational
and industrial exposures, suicide and potential air-, water- and food-borne terrorism agents such as
weaponized gases and liquids. Treatment at this is time is limited and currently depends on supportive care
and use of antidotal therapy of variable effectiveness. The primary cause of death to these mitochondrial
inhibitors is circulatory shock and cardiac arrest. Despite currently available treatments, morbidity and mortality
remains high due to significant gaps in knowledge, including the relationship between mitochondrial
dysfunction in response to acute mitochondrial poisoning and the lack of adequate molecular or cell-based
indices for goal-directed treatment. My long-term goal is to identify characteristic signatures of abnormalities in
mitochondrial bioenergetics and dynamics in human blood cells as well as apply a new pharmacological
strategy of mitochondrial-directed therapy. My central hypothesis, formulated on the basis of my relevant
publications and preliminary data found in this grant, is that there are considerable changes in complex-linked
activity, ROS and dynamics in response to acute poisoning. Also that blood cells may be used a surrogate
marker of mitochondrial dysfunction of affected tissue. At this time there are no clinical tests that directly
measure mitochondrial function in a time-sensitive manner relevant to acute patient care. The experiments
proposed in this application will apply the measurement or assessment of various parameters defining
mitochondrial bioenergetics and dynamics in isolated human blood cells obtained from poisoned patients. We
will also apply a new pharmacologic strategy for mitochondrial directed treatment in human blood cells
exposed to select mitochondrial poisons in a controlled manner. The rationale for the proposed research is
develop a clear understanding of the dysfunction that appears in mitochondrial bioenergetics and motility in
response to mitochondrial poisons and the restoration of normal mitochondrial function that occurs with
implementation of effective treatment.

## Key facts

- **NIH application ID:** 10112290
- **Project number:** 5K08HL136858-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** DAVID H JANG
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $168,696
- **Award type:** 5
- **Project period:** 2018-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112290

## Citation

> US National Institutes of Health, RePORTER application 10112290, Abnormal Mitochondrial Bioenergetic and Motility Signatures in Human Blood Cells as Indices of Acute Poisoning in Patients (5K08HL136858-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10112290. Licensed CC0.

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