Vinicio de Jesus Perez Receives Prestigious Award from ASCI

Vinicio de Jesus Perez

Each year for the past several years, the American Society for Clinical Investigation (ASCI) has presented about 30 Young Physician-Scientist Awards, which recognize medical professionals who are supported by NIH K awards or similar significant career-development awards, are early in their first faculty appointment, and have made notable achievements in their research. For 2016, one winner is Vinicio de Jesus Perez, MD (assistant professor, Pulmonary and Critical Care Medicine), whose clinical and research focus is pulmonary hypertension.

De Jesus Perez’s work runs the gamut from the lab to the clinic, seeking answers in the lab to improve the outcome of the patients he sees in his clinic. “I am interested in understanding the genetic molecular condition,” he says, “and in identifying potential therapies. The ASCI award recognizes my work looking at molecular signaling pathways that control how cells within blood vessels behave during health and disease.”

Pulmonary arterial hypertension is a rare disease that primarily affects young women, presents with right heart failure and, without therapy, leads to death. Most patients present when the disease is advanced, and current therapies -- vasodilators -- are not curative. De Jesus Perez describes his patient population as varying from “a 30-year-old woman after giving birth to her first child to a 40-year-old who rehabilitated herself from methamphetamine to someone with HIV. We have yet to understand why two-thirds of patients with pulmonary hypertension are women. We believe there is a hormonal component playing a role in disease susceptibility, but it’s not entirely understood.”

What is understood is the unfortunate direct relationship between pulmonary hypertension and the use of illicit drugs such as cocaine and, most popularly today, methamphetamine. De Jesus Perez often begins presentations with clips from Breaking Bad, the television series about a terminally ill high-school chemistry teacher in need of money who turns to making and selling meth. To make an important point with his audience, de Jesus Perez goes a step further, also showing faces of meth addicts as the disease takes over because, as he says, “Breaking Bad never showed the actual impact of addiction on the community.”

His patients with meth-induced pulmonary hypertension provided one direction for de Jesus Perez’s work. He explains, “Using gene sequencing data from these patients, we identified an interesting gene called carboxylesterase-1, which seems to be involved in the way the body metabolizes and degrades amphetamine-like compounds. Then we used patient-derived tissue to look at the gene and its product, which is an enzyme, and we found that methamphetamine-addicted patients had much less of the protein and demonstrated reduced signaling activity associated with a mutation. If we can correct that mutation, endothelial cells in the lung might become resistant to damage from methamphetamine and more driven to regenerate after serious injury.”

He continues: “We identified for the first time that when the lung is exposed to methamphetamine the blood vessels have the ability to internalize and metabolize it, which can cause significant damage to endothelial cells. Then those endothelial cells may die out, which will trigger the process that leads to pulmonary hypertension.”

We have yet to understand why two-thirds of patients with pulmonary hypertension are women. We believe there is a hormonal component playing a role in disease susceptibility, but it’s not entirely understood.

Methamphetamine is not the only cause of this incurable disease, although its current popularity puts much greater numbers of people at risk of developing pulmonary hypertension as a result. Because most patients present late in the course of the disease, the available therapies are only able to improve their clinical condition and health for a time. De Jesus Perez likens pulmonary hypertension to diabetes and hypertension “where you take a therapy for life, but those diseases can be controlled by medications and lifestyle changes. Despite the therapies we prescribe, eventually pulmonary hypertension progresses, the medications stop working, and the patients either die or need a transplant.”

The key to better therapies for this disease is understanding its pathobiology first. De Jesus Perez and his colleagues have started there: “We take genetic data from our patient population to mine to identify possible genes of interest related to the pathobiology of pulmonary hypertension. Next we use both animals and cell systems to piece out the relevance of those genes to disease development. Then we make a map to connect the dots to put those candidate genes in perspective. Then we can speculate as to whether one or more genes associated with that pathway may be a druggable target. Next we implement drug development strategies to see if there are compounds out there that can potentially be used.”

There is no shortage of patients with pulmonary hypertension who would benefit from new therapies. “I’ve been taking care of patients who are afflicted with the condition for 16 years,” says de Jesus Perez. “Stanford has the largest pulmonary hypertension center in the United States.”

There is reason to hope the work being done in his lab will help move the needle toward better treatments and ultimately a cure for pulmonary hypertension.