Kimonis Lab at UC Irvine
Collaborating with UC Irvine to Advance Rare Disease Research
At The Lost Enzyme Project, we are committed to transforming the lives of individuals and families affected by Beta-Mannosidosis, an ultra-rare lysosomal storage disorder with no existing treatment. In collaboration with the Kimonis Lab at the University of California, Irvine (UCI), we are conducting groundbreaking preclinical studies to develop an enzyme replacement therapy that could offer new hope for patients worldwide.
About Kimonis Lab
Research for the Lost Enzyme Project will take place at the Kimonis Lab at the University of California, Irvine. Our goal is to raise $520,925 by August, 2025, to fund the preclinical studies and research necessary to move into enzyme development with JCR Pharmaceuticals. These funds goes towards the preliminary work in cell line and animal studies. Your support will keep us going.
The project’s design is intended to support the following goals:
GOAL 1: Clinical characterization and Natural history studies
GOAL 2: Utilization of Fibroblast cell lines for translational (treatment) studies
GOAL 3: Translational studies in neuronal cell lines derived from patient iPSCs (induced pluripotent stem cells)
GOAL 4: Conduct scientific lab work including a mouse model
We thank you for donating to our project. This groundbreaking enzyme replacement treatment will transform the outcomes of people diagnosed with Beta-mannosidosis around the world.
Meet the Kimonis Team
Virginia E. Kimonis, MD
Principal Investigator Division of Genetics & Genomic Medicine
Virginia Kimonis is head of Kimonis Lab at the University of California Irvine. Dr. Kimonis is a Nationally renowned expert, specializing in genetics and clinical biochemical genetics. She is board certified in clinical genetics and recognized as a Physician of Excellence by the Orange County Medical Association.
Prior to joining the Children’s Hospital of Orange County, Dr. Kimonis attended medical school in the UK at Southampton Medical School, completed residency in pediatrics at Massachusetts General Hospital in Boston, and conducted her fellowship training in clinical and biochemical genetics at the National Institutes of Health, John Hopkins and Washington DC Children’s Hospital. She is actively working with the NIH sponsored Rare Diseases Clinical Research. She speaks fluent Hindi and Greek. And she is the lead researcher for The Lost Enzyme Project, a preclinical study aimed at creating a novel treatment for Beta-mannosidosis.
Angela Martin-Rios MD, MSc
Lysosomal Storage Diseases Fellow
Dr. Angela Martin, is a postdoctoral researcher at the Kimonis Laboratory. Her main interest is the inborn errors of metabolism, and her research focuses on lysosomal disorders, Pompe disease and Beta-mannosidosis. Her work on Pompe disease includes therapeutic approaches based on using antisense oligonucleotides.
Her work on Beta-mannosidosis includes a natural history study, studying the biochemical and molecular phenotypes, and potential treatments for the disease. She obtained her Master’s and Medical Degree in human genetics at the National University of Colombia. Outside the lab, she enjoys cycling, crocheting and embroidery, watching movies, reading, and supporting Colombia’s national soccer team.
Dr. Martin is fundamental to the Kimonis Lab and The Lost Enzyme Project. We are so grateful for all the hard work she does to give hope to those affected with Beta-mannosidosis and their families.
Lan Weiss, MD, PhD
Project Scientist
Dr. Lan Weiss is a scientist currently affiliated with the University of California, Irvine. Holding a Doctor of Medicine degree from Hue University, Vietnam, and a Doctor of Philosophy in Human Genetics from Nagasaki University, Japan, Dr. Weiss brings a wealth of knowledge to her current role.
Since joining the Kimonis lab in 2016, Dr. Weiss has dedicated her research efforts to unraveling the pathological mechanisms underlying hereditary diseases such as: Inclusion Body Myopathy associated with Paget disease of bone and Frontotemporal Dementia (IBMPFD) or VCP multisystem proteinopathy, Rimmed Vacuolar Myopathy associated with mutations in the Heat Shock Protein B8 (HSPB8) gene, and Pompe disease.
Her primary objective is to make significant contributions to the development of a cure for these debilitating diseases. Dr. Weiss is particularly enthusiastic about harnessing the potential of Adeno-Associated Viruses (AAV), renowned for their proven safety and efficacy, to deliver therapeutic genes specifically to the affected muscles—the primary organ impacted in many related patients. Additionally, she actively explores the realm of antisense oligonucleotides gene editing to restore or improve muscle function.
Her research unfolds across two pivotal pre-clinical platforms: Patient-induced pluripotent stem cell (iPSC)-derived skeletal muscle progenitor cells and the disease mouse models. This multidimensional approach reflects her dedication to advancing the comprehension and treatment of devastating conditions.
Pallabi Pal, PhD
Project Scientist
Pallabi is a Project Scientist at the laboratory of Dr. Virginia Kimonis at UC. Her research focus on therapeutic strategies of genetic neuromuscular disorders. The underlying mechanisms and the treatment for hereditary inclusion body myopathies associated with Valosin Containing Protein (VCP) and Heat Shock Protein B8 (HSPB8) associated rimmed vacuolar myopathies associated with muscle atrophy and early demise remain to be elucidated.
To investigate in vitro the molecular mechanism of VCP and HSPB8-associated myopathy and to assess the potential of new treatments, patient iPSC-derived myoblasts are utilized.
She is recapitulating the pathogenic phenotype of patient-derived iPSCs differentiated into muscle cells. Currently, she is assessing the beneficial effects of antisense oligonucleotides (ASO) in patient iPSC derived VCP myoblasts for amelioration of effects on dysfunctional morphology, bioenergetics and biological processes. Additionally, compounds that stimulate autophagy favor the removal of protein aggregates.
She is currently using an autophagy modifier to facilitate removal of protein aggregates by stimulating the autophagy pathway. Successful completion of the present mechanistic and translational study will pave the way for the treatment of HSPB8-associated inclusion body myopathy and will also benefit other related disorders.
Alyaa Shmara, MD
Postdoctoral Research Scholar
Alyaa is a postdoctoral fellow at the laboratory of Dr. Virginia Kimonis at UCI. Her research focus is unraveling the mechanisms underlying hereditary inclusion body myopathies associated with Valosin Containing Protein (VCP) and Heat Shock Protein B8 (HSPB8) mutations. She is heavily involved in investigating therapeutic approaches using FDA approved medications, small molecules, and gene therapy with potential to ameliorate pathology in myopathy mouse models.
She also conducts clinical research in Lysosomal Storage Diseases and has completed a Lysosomal Storage Diseases fellowship at UCI’sDepartment of Pediatrics, Division of Genetics and Genomic Medicine from 11/2021-12/2022.
Her research focus was to investigate the prevalence of low bone mineral density in patients with Fabry disease. She is currently serving as a patient advocate for a rare disease organization, Cure HSPB8 myopathy, and leading the effort of raising awareness and increasing patient identification of this rare disease.
Contact UCI Health
David López
Director of Development
UCI Health Advancement
714-456-6226 (office)
562-273-8281 (cell)
davidfl@hs.uci.edu
3800 West Chapman Avenue, Suite 3300
Orange, CA 92868
