Funding the Next Generation

2024 accelerators winner

Sara Carli

Kristen G. Navarro, PhD

Children’s Hospital of Philadelphia

Dysregulation of MTORC1 in Human Cell Models of Mitochondrial Complex V Deficiency 

Project Summary

Cells must adapt to their environment to grow and survive. The process of the cell learning about its external environment, for example nutrient availability, health of surrounding, etc. is called cell signaling. Cell signaling is usually conducted inside the cell by a series of specific proteins that talk to each other in a set order, to relay information from outside the cell to the cell itself to allow the cell to make decision about how to adapt. One recipient of this information in the cell may be the mitochondria. Mitochondria are responsible for energy production and are intimately involved in cell signaling pathways. To make energy, proteins in the mitochondria called Mitochondrial Complex proteins use a type of cellular electricity known as electrons to pass electrical energy to their neighbors in a line back and forth. At the very end of the line, a protein called ATP Synthase (also called Mitochondrial Complex V – CV) produces energy. In mitochondrial disease when mitochondria do not work properly, cell signaling, and the ability of the Mitochondrial Complex proteins are disrupted. Signals that were designed to be temporary ‘mitochondrial overwhelm’ signals may stay on permanently. Since mitochondrial diseases can be caused by multiple different abnormalities in the mitochondria, developing universal treatments is difficult. This proposal aims to study a specific mitochondrial disease called ATP Synthase (Complex V deficiency) and how it interacts with the mTOR pathway, one of the main cell signaling pathways to communicate nutrient availability. This work builds on the discovery that the mTOR pathway is abnormal in animal models of Complex V deficiency and that mTOR directly inhibits complex V in healthy animals. This work could help future researchers to develop and direct precision treatments for mitochondrial disease that manipulate cell signaling pathways.

2024 accelerators finalists

Filomena Massa

Raquel Justo-Méndez, PhD

IRB Barcelona

Implications and Novel Therapeutic Insights on Mitochondrial Integrity in Hematopoiesis and Immune Balance in the Context of Mitochondrial Diseases

Project Summary

This research investigates how important cells called multipotent progenitor cells, which play a crucial role in creating different blood cells in our body, stay healthy. These cells exhibit an efficient energy management system, but mutations in the mitochondrial DNA can impact on the organelle quality control mechanisms, resulting in issues with the maintenance and differentiation processes of these cells. Additionally, mutations in the mitochondrial genome of mature blood cells and the resulting inflammation can harm the health of the different organs. Such concerns are particularly significant in individuals with mitochondrial diseases. By studying different mouse models that mimic these health conditions and blood cells obtained from healthy donors and patients, our goal is to gain a deeper understanding of these complexities. This project aims to help individuals with similar health challenges by developing new ways to diagnose and treat them effectively.

Leonard Burg

Daniel Lagos, PhD

University of Cambridge

Unveiling the Role of Secreted Mitochondria in Extracellular Vesicles: Implications for Primary Mitochondrial Disease

Project Summary

Mitochondrial diseases manifest with a wide range of symptoms, affecting various organs and tissues in our bodies. Thanks to technology, scientists have identified most of the DNA mutations responsible for these diseases, yet we still do not fully comprehend what determines this diversity. One cellular adaptation mechanism to cope with the accumulation of defective material inside cells is the secretion of this damaged content in the form of vesicles. These vesicles can be taken up by neighbouring cells or cells located at distant sites enabling a broader effect. Furthermore, it has been observed that these vesicles can carry mitochondria, which may have negative effects on the recipient cells. The objective of my project is to study these vesicles by characterizing their number, content, and effects on neighbouring cells, focusing on cell types typically most affected in mitochondrial diseases, such as muscle cells and neurons. The results of the experiments in cellular models will be confirmed and validated in blood samples of patients with mitochondrial diseases. I believe that the proposed research will reveal new ways how mitochondria can participate in communication between different cells in the body, potentially improving cell survival and future therapy development in mitochondrial diseases.

Become an accelerator

Your Involvement Matters

Innovation, speed and agility are key to finding effective treatments for mitochondrial disease.  Your support is the beginning.  Accelerating the research could lead to a cure.

Our accelerators are engaged philanthropists.  Through our annual livestream-pitch event, our members have the opportunity to cast their vote for the project they feel the most passionate about, and ultimately see the difference their contribution makes.

How It Works

UMDF earmarks the accelerators 
prize

h

Grant applications submitted by promising post-doctoral fellows

 

Applications reviewed and finalists selected by UMDF Scientific and Medical Advisory Board

3-5 finalists prepare “fast pitches” to be broadcast live at UMDF Conference

 

Z

Each accelerator 
casts a vote for the project they feel most passionate about

Prize awarded to winner

Right now… a researcher in a lab believes her theory could cure mitochondrial myopathy.

Right now… a scientist believes his innovation may bring about an end to Leigh syndrome.

Right now… people affected by mitochondrial disease need energy…and YOUR energy can help….but we need to go fast.

It could be an innovation that will find the cause of mitochondrial disease. Or, it may be the research that develops an effective treatment. Now is the time to accelerate that science from bench to bedside. Our patients and families are counting on your energy to help UMDF move faster toward a cure.

When you give $500 or more (cumulatively in a year), you unlock your accelerators benefits! No matter how you give – through a special event, to a designated fund or as a tribute to a patient – when you reach the accelerators level you join a group of engaged philanthropists. You will get a first-hand look at the promising ideas being developed in mitochondrial disease research.

2023 Prize Winner

Sara Carli

Conor Ronayne, PhD

Dana-Farber Cancer Institute,
Harvard Medical School

Project Summary
Energy is made in our cells in structures called mitochondria. Mitochondria were born when an ancient cell combined with a bacterium. A relationship formed and the cell held on to the bacteria to use it to make energy. Antibiotics are drugs that are used to treat bacteria. Mitochondria can also be affected by these drugs. Ailments are caused from damaged mitochondria resulting in diseases in the brain and muscles. These ailments are called mitochondrial diseases and currently have no therapies. Our lab discovered that antibiotic drugs can treat these ailments in cells and mice. In this application we propose to explore exactly how these drugs work in the cell and in the brain. We will do so by performing experiments to test hypotheses based on the observations made by our lab and others in the field. This proposal will identify how these drugs rescue mitochondrial diseases. The experiments will identify new ways that cells survive and provide new ways to treat these diseases. This will open up a new field in mitochondrial biology and will impact mitochondrial disease. The drugs used in this application are already used in the clinic and approval for mitochondrial disease will be fast. This proposal will impact our understanding of the disease and how it harms cells and tissues and will also provide a new way to treat these diseases in the clinic.

2022 Prize Winner

Sara Carli

Sara Carli, PhD

Università di
Bologna, Italy

Project Summary

Mitochondria have their own genetic material, the mitochondrial DNA (mtDNA). Having too little mtDNA is one of the causes that drives the onset of Mitochondrial Depletion Syndromes (MDSs). Patients with MDS experience a spectrum of symptoms which generally lead to death in a few months. mtDNA depletion could be due to a defect in the production of a primary building block or gene of the mitochondrial DNA. Currently, there are no animal models present to better understand MDS or to test the effectiveness of therapeutic treatments. This project proposes to create a mouse model that will be used to better understand the progression of MDS. With a mouse model available I will then test the effectiveness of gene therapy, an innovative therapeutic approach to restoring the defective gene that causes MDS. 

2021 Prize Winner

Lia Mayorga, MD, PhD

IHEM
Mendoza, Argentina

Project Summary
Human cells have two types of DNA, nuclear and mitochondrial DNA. The latter controls energy production for the body which is essential for life. Each cell has many mitochondria to generate sufficient energy for our organs, and inside each mitochondrion, there are many copies of mitochondrial DNA. In patients with certain types of mitochondrial diseases, the mitochondrial DNA copies are not identical, resulting in a mixture of defective and normal copies. The defective copies lead to poor mitochondrial function and disease, so the more defective vs. normal copies a cell has, the worse the disease symptoms. Our goal is to develop a method to selectively reduce the number of defective mitochondrial DNA copies, leaving mostly normal ones. Gene therapy strategies that have worked for nuclear DNA defects have not reached clinical trials for mitochondrial genes because the mitochondrion is very selective as to what can or cannot enter the organelle. We propose a different approach taking advantage of the cell’s natural communication between the nucleus and mitochondria. Previous work has shown that intense mitochondrial dysfunction, such as the one present in cells with mostly defective mitochondrial DNA, produces modifications to nuclear DNA (not in sequence, but in function) that perpetuate the survival of such unhealthy cells and sustain disease symptoms. Consequently, we plan to modify these nuclear DNA modifications that exist in dysfunctional cells to “select” cells with the less defective mitochondrial function. This nuclear DNA modulation technique is already used to treat other illnesses, which increases the possibility for it to reach clinical trials in less time.

2020 Prize Winner

Kinsley Christopher Belle

Stanford University
Stanford, CA

Project Summary
Mutations in mitochondrial DNA result in an array of disease which can be found in nearly all tissue types of the human body. Furthermore, these mutations can exist in varying states of prevalence due to a rare phenomenon known as heteroplasmy. Heteroplasmy is the percentage of mutant mitochondrial DNA within a cell, tissue, or organ system.  The level of heteroplasmy or the percentage of mutation directly correlates with disease and cellular dysfunction. 

Our objective is to determine how internal factors, such as development and cell specification cues, as well as external stimulus, oxygen levels, energy substrates, and drug compounds influence mitochondria heteroplasmy. Our preliminary assessments suggest that cell-type development and cell division influence heteroplasmy in developing tissues, additionally our work on cell conditions, and small molecules has yielded promising preliminary results for possible therapeutics. This body of work serves as a template for discovering compounds that reduce mitochondrial heteroplasmy and thus disease burden in patients.

2019 Prize Winner

Arwen Gao

Ecole Polytechnique Federale de Lausanne (EPFL)
Lausanne, Switzerland

Project Summary
Dr. Gao was awarded a $50,000 prize for her project entitled Identification of Novel Compounds to Treat Rare Mitochondrial Diseases. The goal of this research project is to identify novel compounds that increase the amount of mitochondria and/or activate the identified pathway in lab-based cell models. The compounds that work best in the cell models will be subsequently tested in animal models of mitochondrial disease. Future work with top compound candidates have the potential to pave the way towards the development of novel drugs targeting rare mitochondrial diseases.

Scientists who are working fast toward a cure.

Vamsi K. Mootha, PhD

HARVARD MEDICAL SCHOOL • Boston, MA

“In 2004, I was a recipient of a $90,200 UMDF grant designed to support my efforts on using computational genomics to identify novel assembly factors for mitochondrial oxidative phosphorylation. With this support, I was able to recruit and hire a talented computational biologist, who proceeded to predict the mitochondrial proteome using a computational tool that led to the identification of several new disease genes, forming the basis for my lab’s first NIH grant.”

Anna-Kaisa Niemi MD, PhD

RADY CHILDREN’S HOSPITAL • San Diego, CA

“A UMDF Clinical Fellowship Award allowed me to focus on diagnosis and treatment of patients with confirmed or suspected mitochondrial disorders. The most impactful part of the fellowship for me was learning about the daily life of children and families affected by mitochondrial disorders. I now continue to use the knowledge and experience I gained that year in my work caring for critically ill infants with confirmed or suspected mitochondrial disorders.”

Michael J. Palladino, PhD

UNIVERSITY OF PITTSBURGH • Pittsburgh, PA

“In 2006, I received a $98,000 research grant from UMDF. This grant funded my research to further develop our Drosophila NARP/MILS model and allow our first venture into compound screening to identify specific drug therapies for mito patients. This award served as “bootstrap funding” helping me successfully apply to the NIH for support of numerous projects and helped secure more than $2.75M in NIH funding for mito research in my lab.”

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