Valerie Arboleda
Valerie Arboleda earned the Toffler Scholar Award in 2023 at UCLA
Biography
Valerie Arboleda was born in Los Angeles, California, to immigrant parents from the Philippines. Her parents were trained as physicians and moved to California to pursue board certifications and a better life. Dr. Arboleda spent the first year of her life in California before her family moved to Chicago. The family braved the cold Chicago weather — a stark contrast to their tropical homeland — while completing their residencies in internal medicine and pediatrics. After completing their training, Dr. Arboleda's parents returned to California, settling near Pasadena. Their family grew and Valerie became the eldest of five children.
Dr. Arboleda was a quiet child and didn’t come out of her shell until high school. She enjoyed playing tennis with her father and was passionate about music and art, particularly playing the piano. In school, she excelled in math and science. After high school, Dr. Arboleda wanted to get as far away from the West Coast as possible. Because she spent all of her formative years in California, she wanted to experience a different location. She succeeded, attending Columbia College in New York.
In college, Dr. Arboleda disliked memorization, particularly in biology, and preferred classes like physiology where she could reason through tough problems. The turning point in her career came when she participated in a summer undergraduate research fellowship and worked in a lab under M.D., Ph.D. physician-scientist, Dr. Carol Troy. Dr. Troy was a neurologist and decided not to practice in a clinical setting but devote her time to Alzheimers’ and demential research. This experience changed Dr. Arboleda’s perspective on what a physician or physician-scientist could do. Dr. Arboleda completed her Bachelor of Arts in biology.
Looking ahead, Dr. Arboleda considered different career paths, including nursing and dentistry, but ultimately decided on medicine. She was thrilled to be accepted into the University of California Los Angeles (UCLA) on the MD-track. Her mentor, Dr. Troy, informed her about programs where she could take a year out of medical school to do research and after two years of medical school,
Dr. Arboleda couldn’t shake the feeling of wanting to conduct research. She took a leave of absence from medical school to work in UCLA’s genetics department, funded by the Howard Hughes Medical Institute and ultimately transferred into the UCLA Medical Scientist Training Program.
Dr. Arboleda’s research experience coincided with the completion of the Human Genome Project. She took part in projects sequencing the small regions of genomes within multiple members of large families to identify the mutation that caused disease within the family. She found the work exciting. The early 2000s marked the beginning of next-generation whole genome sequencing, a field that has since revolutionized biological and medical research. Five years later, Dr. Arboleda finished her Ph.D. and returned to medical school. Upon completion of residency training, she became a board-certified pathologist focused on genetic disease diagnosis.
Today, Dr. Arboleda is an Associate Professor of Pathology and Laboratory Medicine at UCLA. Along with her research team, she is working to understand how various genetic modifications impact the functionality of human genes and influence the molecular phenotype at the cellular level. By deciphering the fundamental role of a genetic mutation, Dr. Arboleda and her team can pinpoint potential targeted treatments for a diverse range of clinical conditions.
“Seeing what an MD could be that was different from what I had seen in my parents’ private practice made me realize that I could have a career in which I could conduct research and be happy. My mentor at the time, Carol Troy, had an MD-Ph.D. and was running a research lab. She didn't do as much clinical time, if any. She enjoyed what she did and loved the science piece.”
- Dr. Valerie Arboleda
“Seeing what an MD could be that was different from what I had seen in my parents’ private practice made me realize that I could have a career in which I could conduct research and be happy. My mentor at the time, Carol Troy, had an MD-Ph.D. and was running a research lab. She didn't do as much clinical time, if any. She enjoyed what she did and loved the science piece.”
- Dr. Valerie Arboleda
Research Focus
Challenges
The World Health Organization estimates that 70 to 80 million people worldwide live with a monogenic disease. Examples include cystic fibrosis, sickle cell anemia, Marfan syndrome, Huntington’s disease and Duchenne muscular dystrophy.
Monogenic disorders are caused by a single gene and can be inherited in several ways, including autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and Y-linked patterns. The type of inheritance pattern depends on the location of the gene on the chromosomes and whether the gene mutation causes disease when one or both copies are mutated.
Dr. Arboleda and her team work directly with patient communities to understand their conditions and seek treatments.
Focus and Priorities
Dr. Arboleda’s research is focused on understanding the mechanisms of certain genetic syndromes at a molecular level, particularly those that involve genes important in organizing DNA in the nucleus. Her lab team is interested in how these genes control the tightness of DNA winding and gene expression, which is crucial for the epigenome.
Dr. Arboleda works with Dr. Bianca Russell, a clinical geneticist, to focus on syndromes such as KA6A syndrome, Bohring-Opitz syndrome caused by the ASXL1 gene, and a syndrome caused by the BRPF1 gene. They use patient-derived stem cells to study how these genes affect different tissues. These stem cells can be transformed into various cell types, such as heart cells, brain cells, or muscle cells, allowing them to observe the gene’s effects in different contexts.
Benefits
Dr. Arboleda hopes findings from laboratory experiments can be translated into potential treatments. If progress comes from conducting small molecule drug screens in a lab setting, then her research team can start testing with mouse models.
Dr. Arboleda’s team is bringing in mouse models with specific patient mutations because they believe the exact mutation is important. These mouse models offer several advantages. Firstly, they can have many mice, allowing for replication of results to demonstrate uniformity. Secondly, they can examine different stages of early development, which is not possible in humans.
This allows them to observe what happens very early during embryonic development in mice and to see the effects of removing the gene in one tissue versus all tissues early on. The aim is to distinguish between the effects directly caused by the gene itself and the ripple effects caused by the absence of that gene at the right time point.
Karen Toffler Charitable Trust Investment
Funding from the Karen Toffler Charitable Trust will support the work of senior graduate students who have experience conducting functional experiments. They will begin treating different cells with known epigenetic modulators using drugs already on the market to treat cancer. These drugs are known to influence the epigenome. Dr. Arboleda’s goal will be to see if they can modulate the genomic effects.
Karen Toffler Charitable Trust Investment
Funding from the Karen Toffler Charitable Trust will support the work of senior graduate students who have experience conducting functional experiments. They will begin treating different cells with known epigenetic modulators using drugs already on the market to treat cancer. These drugs are known to influence the epigenome. Dr. Arboleda’s goal will be to see if they can modulate the genomic effects.
“We spent the last five years trying to build a system where we can study different disorders in a very comprehensive way using genomics and functional genomics. Now we're trying to see if we can treat it in some meaningful way.”
- Dr. Valerie Arboleda