The Research

Meet the Lead Researcher Virginia Kimonis, MD

Dr. Virginia KimonisDr. Kimonis is privileged to serve as a clinician Scientist in the Division of Clinical and Biochemical Genetics, UC Irvine and CHOC. She received her medical degree from Southampton Medical School, UK and completed residencies in pediatrics and general practice in the UK before moving to the US. She completed a residency in pediatrics at Massachusetts General Hospital, Boston and fellowship training in clinical and biochemical genetics at the National Institutes of Health, Johns Hopkins and Washington D.C. Children’s Hospital. Prior to her move to UC Irvine in 2006, she worked at Boston Children’s Hospital and Southern Illinois University School of Medicine. She is board certified in Clinical Biomedical Genetics, Clinical Genetics and Pediatrics.


Dr. Kimonis’ NUPBL research includes creation of a conditional knockout mouse in which researchers inactivate or “knock out” an existing gene specifically in the brain of the mouse. Knockout mice are important animal models for studying the role of genes which have been sequenced but whose functions have not been fully determined. We predict this loss of the gene activity will causes changes in the mouse’s appearance, brain structure, behavior and other observable physical and biochemical characteristics.  Since we still do not fully know what the NUPBL gene does this type of research is the best option for observing differences from normal behavior or brain activity,. The mouse model will accelerate new treatments for patients with NUPBL disease and other more common disorders.


Download Dr. Kimonis’ full bio: Click Here

Thank you for your support. Your tax-deductible gift directly funds research into the NUBPL gene. We hope this work leads to new treatments and a cure for Complex I Deficiency, and that it might also provide answers about other conditions associated with the gene, including Parkinson’s Disease.

Research Update

Virginia Kimonis, MD
Especially Beautiful Fundraising Update
November 2017

NUBPL is a “rare” mitochondrial disease.  Research activities represent hope for the lovely Spooner girls and others with this rare condition. In fact, the field of clinical genetics represents a promising pathway to new and better treatments for many rare diseases. And, what this means is that every child with NUBPL disease today has a reason to hope. Nothing is more thrilling than to successfully slow or treat a disease.

With the funds we have completed the following studies:


Phase 2

  1. The Kimonis Laboratory has studied the skin fibroblasts from the girls for the mitochondrial function at UC Irvine using the Seahorse instrument in collaboration with Dr. Christina Kenney’s lab.
  2. We have studied the effect of paraquat a mitochondrial complex 1 poison and hydrogen peroxide to the cells in order to study mitochondrial function under conditions of stress and have found differences between the patients and age matched controls.
  3. Moyra Smith and Ambry have completed the reanalysis of the exome data in the two girls to understand the cause of the differences between the two girls. No further differences have been identified.
  4. Our collaborator, Janneke Balk, at the University of East Anglia, UK, has shown in her lab that treating yeast cells with peptones improves mitochondrial function. Therefore, we now recommend treating patients with NUBPL disease with a high-protein diet. As a result of our collaboration Dr, Balk has treated the cells and yeast mutants with components of the mitochondrial cocktail to identify specific drugs that may be beneficial. She has identified that coenzyme Q10 treatment has resulted in improvement in the activity of mitochondrial complex 1. She has also introduced the various mutations found in patients in the yeast in order to study the effect on mitochondrial complex 1 in order to conclusively establish that the mutations are the cause of the disease.
  5. We have presented several posters and are completing the manuscript for publication on the 5 new patients in 4 families with NUBPL disease. Dr. Kimonis has contacted the exome abs in order to identify other patients and families with NUBPL disease.
  6. Peggy Eis/Eli Hatchwell of Population Diagnostics update.


Phase 3 ($ 20,000 raised from the Especially Beautiful event in 2016)

  1. Stem cell line has been made with skin fibroblasts from Calynn, Ryann and Patient 3 by Dr. Schwartz, CHOC Children’s as a collaboration ($5,000 requested by Dr. Schwartz for supplies). These stem cells have made into brain neuron cells to study the effect of the mutations in the gene.
  2. Bethany Berg, genetic counseling intern for her thesis (attachment) has performed RNA studies to identify the splicing variants resulting from the Spooner mutation. The Patient 3 splicing mutation analysis was not successful.
  3. CRISPR mouse model has been created:The animal model we hope will be the best and most authentic model and will allow us to actually study the brain in NUBPL disease.  Mice share 99% of the human genetic makeup, and have proven to be a very useful model of the human disease based on experience in Dr. Kimonis’ lab for the past seven years. The approximate cost to just make a mouse model is $ 10K (see attachment)
    We can perform imaging of the brain in order to study the impact of manipulating the NUBPL gene on the mouse cerebellum, balance and cognitive function.  We then plan to study the effect of a drug panel on the structure and function of the brain in order to identify potential novel treatments that could be tried in children with NUBPL disease.Expenses:
    Stem cell work                                            $5,000
    CRISPR mouse                                           $10,000
    Supplies for  RNA splicing, Seahorse     $3,000
    Balance:                                                        $2,000


Phase 4— (Goal $ 50,000)

  1. CRISPR Mouse Research (research costs—supplies, animal housing, personnel, etc.)a. Experiments to be conducted (breeding mice, behavior studies, study of cerebellum, study of the expression of the gene,)b. Test different treatments (drugs) to improve the cells and the structure of the brain of the mice.

    Because the specific Spooner c.311T>C (p.L104P) gene mutation is a severe mutation  it is  possible that introducing this gene mutation will also be lethal in animals,

  1. EMMA Mouse project: As a result of further research I have identified a mouse model that is embryonic lethal by E12l. It is expected the mouse will show the typical clinical features such as the cerebellar atrophy. Currently there is almost no information on the brain pathology and function in this disease. These mice can be a useful resource for future mechanistic and therapeutic studies.If the CRISPR mouse is lethal I plan to use technology to only knock out the gene in specific parts brain to study the effect of NUBPL deficiency.


  1. iPSC derived neuron cells will be used to study mechanism and the effect of novel treatments by studying gene expression and further mitochondrial studies such as the Seahorse.. Stem cell work is very intensive and expensive however the potential rewards are enormous because the personalized medicine work is done using cells from the girls.
  2. We are working with Pat Jennings, UCSD on understanding the chemistry of NUBPL iron clusters.
  3. Janneke Balk is continuing to work on mitochondrial complex 1 activity with NUBPL mutations.

Other Research

Thank you for your support. Your tax-deductible gift directly funds research into the NUBPL gene. We hope this work leads to new treatments and a cure for Complex I Deficiency, and that it might also provide answers about other conditions associated with the gene, including Parkinson’s Disease.

Contact Us

The more we connect with other NUBPL families, the closer we get to finding a cure.  Do you have NUBPL or do you think you may?  Or, are you a researcher who is interested in studying NUBPL?  Please contact us.  We want to hear from you. Although some families are public about their journey, we respect your desire for privacy.

    First Name (required)

    Your Email (required)

    Your Message