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When Dr. Anand K. Ganesan started a vitiligo specialty practice in 2018 at the UCI Health Beckman Laser Institute & Medical Clinic, it was to find new therapies to reverse the disfiguring skin disorder.

Vitiligo — pronounced vit-ill-EYE-go — causes white patches, often on the face and hands, the result of the immune system destroying the skin’s pigment-producing cells.

“All we had at the time was light therapy and topical steroids, which were minimally effective,” says Ganesan, a UCI Health dermatologist and vitiligo expert who was keenly aware of the emotional and psychological toll the disease had on his patients, many of them vulnerable young children and teens who withdrew from peers rather than risk ridicule or worse.

Today, there has never been more hope for patients with the autoimmune disease, which affects an estimated 70 million people worldwide, at least 25% of them children, says the UCI School of Medicine professor of dermatology and biological chemistry.

New options

A topical cream called ruxolitinib, is the first therapy approved by the U.S. Federal Drug Administration (FDA) that restores pigment in vitiligo patients. The FDA also recently gave breakthrough device approval for RECELL®, a one-time therapy using the patient’s healthy cells to stimulate lasting repigmentation in stable vitiligo, the regenerative medicine company Avita Medical announced June 16. Other topical, oral and injectable medications also have shown success at halting progression of the disease in early phase trials.

Ganesan and his team of clinicians and researchers have been directly involved in studying all these therapeutic breakthroughs. In addition, they used genomics and UC Irvine’s powerful microscopy resources for a novel study that reveals how immune cells, pigment-making melanocytes and keratinocytes — cells that give skin its structure — interact to maintain depigmented areas. The study was led by UCI Health dermatologist Dr. Jessica Shiu, who, along with Ganesan, is among a handful of U.S. physician-scientists to conduct National Institutes of Health-funded vitiligo research.

“We have made a lot of progress, but there is still a lot more work to be done,” says Ganesan, who recently was honored by the American Skin Association for his pioneering research on vitiligo.  “While many of these new therapies work for patients with disease on the face, they don’t work well on other parts of the body, especially the hands, which is equally distressing for patients.”

Raising awareness and support

As international experts, patients and prominent advocates for improved vitiligo care converge in Atlanta this week for a three-day conference to mark the 13^th annual World Vitiligo Day on June 25, Ganesan and his team have launched a campaign to raise awareness about the disease, fund a dedicated dermatology fellowship and provide patients with additional resources to cope with their condition.

Learn how to support vitiligo care and research at UCI Health ›

Ganesan first began treating vitiligo patients as a dermatology resident at University of Texas Southwestern Medical School in Dallas under the guidance of internationally regarded vitiligo expert Dr. Amit Pandya. Armed with a PhD in microbiology and molecular genetics as well as a medical degree, the young resident was already interested in melanocytes, cells found in skin and hair that produce pigment.

“Vitiligo is unique,” he says. “In other skin diseases like psoriasis or eczema, you treat the autoimmune component to stop the body from attacking the cells and the disease resolves itself. I was struck by this disconnect. Patients with vitiligo had melanocytes but they weren’t working to repigment the white patches.”

More than a skin disorder

Equally distressing is the disease’s effect on emotional and mental health. “When patients first come to me, many of them are down, dejected because they’ve been told no effective treatments exist for their disease,” he says. “This is why advocacy is so important. Both physicians and patients need to know that viable therapies are available.”

An estimated 30% to 50% of vitiligo patients suffer from depression, which in rare cases may even result in suicide attempts. It’s one of the reasons Ganesan helped launch a UCI Health vitiligo support group, to provide a safe space for patients to share treatment experiences and discuss coping strategies for daily living, such as makeup and clothing tips. To understand the impact of the disease, he recommends viewing the 2016 video “Vitiligo: Truth Hope and Change,” which was filmed in part in Orange County with support from UCI.

“When people actually start getting better, their perspective changes,” he says of his patients, a number of whom participated in the vitiligo trials and have seen improvement, “It’s the most rewarding thing for me, to see that spark come back in their eyes.”

Hand spots harder to treat

The new topical treatment restores pigment on the face in about 60% of patients, although it isn’t as successful for the rest of the body. “Hands in particular don’t seem to respond to any of the newer therapies, which is very distressing to the patient,” he says.

New oral therapies also show promise in stopping disease progression. These treatments, which target the Janus kinase signaling pathway, suppress the body’s T-cell defense systems and may result in long-term side effects.

“It’s not perfect,” he says of the new oral therapies. “But it’s a start and hopefully we can improve on them with more research.”

Great strides also have been made in skin-grafting techniques and light therapy to stimulate repigmentation. The RECELL treatment involves harvesting the patient’s healthy melanocytes from a small amount of skin, which is processed to create a solution of skin cells that are applied to white patches of skin prepped by laser ablation. The treated area is then covered with a dressing that allows the solution to “stick” to the grafted site.

Studies showed that more than a third of RECELL participants saw greater than 80% repigmentation 24 weeks after treatment, while over half of patients saw greater than 50% repigmentation over the same period.

Making treatment more accessible

The hope is that RECELL will become a procedure any dermatologist could perform with very limited training, Ganesan says. “It does require a laser to ablate the skin, but it’s a laser that most dermatologists already have in their office.”

Light therapy, too, has become more accessible. Treatments that required intensive daily or weekly office visits now can be done at home. “We give patients a light box and teach them how to use it,” he says. “Light therapy treatments are really hard on children because you have to go into the box two or three times a week.

“One patient I’ve been treating since she was about 8 years old is a teenager now. Being able to do the treatment at home has been a godsend!”

With the white patches gone from her face and about 60% to 70% of her body, he says she is now an outgoing student who participates in school and extracurricular activities with confidence.

Ganesan has a lot to share at the next quarterly vitiligo support group meeting, which went on hiatus during the COVID-19 pandemic.“We want to let our community know about the exciting new treatments available, about our research and how we are expanding our research team,” he says.

“One of the most fulfilling things we do is work with our patients to learn how they are affected by the disease. We use that information to design better treatments for them.”

Anand K. Ganesan, MD, PhD, is a board-certified UCI Health dermatologist who specializes in skin cancer and skin pigmentation disorders, including vitiligo, melasma and albinism.

A prolific physician-scientist, Ganesan explores how melanocytes respond to environmental cues, such as ultraviolet radiation and inflammation, to maintain normal homeostasis and how that homeostasis is disrupted by diseases processes, including melanoma and vitiligo. His work spans the spectrum from basic laboratory studies to clinical trials as he seeks to develop novel approaches to diagnosing and treating disease.

He is a professor of dermatology and biological chemistry at the UCI School of Medicine, where he serves as associate dean for physician-scientist development. He also co-directs the Chao Family Comprehensive Cancer Center’s programs in Biotechnology, Imaging and Drug Development and Molecular Diagnostics and Therapeutics. He is the author or co-author of dozens of peer-reviewed publications, including the recent https://www.ucihealth.org/news/2022/04/uci-researchers-discover-promising-new-molecule-for-cancer-therapy” discovery of a new class of drugs to potentially treat melanoma and other cancers.

Click here to view the full UCI Health “Live Well” article.

Wilder-Smith’s Clinical Studies Inspire Participants’ Career Aspirations

Dr. Petra Wilder-Smith, UCI Beckman Laser Institute & Medical Clinic’s Director of Dentistry, serves low income dental patients in Orange County and abroad through the use of her innovative, portable oral cancer screening device and other breakthrough technologies.  A strong advocate for preventative medicine and educating populations about proper oral health, the research arm of her practice takes place at the Institute.

With over 400 subjects enrolled in more than 40 Institutional Review Board (IRB) clinical research protocols conducted by Institute researchers annually, Dr. Wilder-Smith has recruited participants for various studies.  These studies include evaluating revolutionary dental products and technologies.

Over the past few years, San Juan Capistrano resident Joey Coleman has been a steadfast participant in Dr. Wilder-Smith’s studies.  Through Dr. Wilder-Smith’s advocacy, Joey has learned about the importance of maintaining good oral hygiene through the use of effective dental products and the avoidance of harsh chemicals with the potential to cause tooth and gum decay.

“Some of my family members have not taken care of their teeth, which has always worried me,” stated Joey. “I have learned a lot more than I ever expected from Petra and her team of doctors, especially when it comes to oral and throat cancer.”

Joey has witnessed Dr. Wilder-Smith’s specialized care.  “Petra is approachable and always willing to share her expertise,” continued Joey.  “I have encouraged my friends and family to join her studies with many who have consistently participated.”

“Joey has raised awareness of UCI’s research within the Orange County community through his enthusiasm and passion for knowledge transfer and innovation,” stated Wilder-Smith.  “He has built bridges to local schools and colleges, encouraging friends and family to learn more about UCI and to join in the many research and educational opportunities provided by the university.”

A few of Joey’s friends have viewed their participation in the studies as transactional.  However, as a former high school baseball player and coach, he realized how pertinent oral cancer prevention was to him and those in his circle.

“Tobacco is a problem in baseball with many players regularly chewing tobacco and using various other nicotine products,” said Joey. “After learning about the consequences, I have shared the harmful effects of use, including tooth loss and gum decay with fellow players – especially with the younger players who I coached.”

As an aspiring attorney, Joey experienced other benefits from working with Dr. Wilder-Smith’s group.  “After learning about my interest in law, Petra introduced me to UCI Law students who served as consultants on her device patents and other intellectual property,” said Joey.  “I found enthusiastic mentorship from the UCI Law students, and gained a plethora of knowledge about the legal profession, including a valuable understanding of the cross-disciplinary pathway that leads from an initial idea to technology innovation that will ultimately improve health outcomes for all.  I learned that this journey encompasses a wide range of legal knowledge and specialties, ranging from patent law and trademarks to regulatory and safety, licensing, investment and contractual expertise.”

From interacting with the law students, Joey’s passion for the legal profession grew.  He is currently working with three different law firms and has since applied to law school, including UCI – his top choice.  Joey’s future career ambitions include working for a law firm or serving as an in-house counsel for a corporation.

“Petra and her team provide dental care to those who are underserved,” stated Joey, “With so many disadvantaged people in Orange County, I strive to launch a venture fund to assist those who are less fortunate in our community.”

“I hope that Joey’s exposure to scientific research and technical innovation through our studies will serve him well as he moves ahead with his lifelong dream of becoming an attorney focused on technology innovation and implementation,” stated Wilder-Smith.  “Wherever life takes him, I know that he will be a phenomenal success and I look forward to celebrating his many accomplishments in the years to come.”

Click here to learn more about Dr. Petra Wilder-Smith.

PI: Yama Akbari, MD, PhD
Co-I: Michael Rochon-Duck, MD

Brain-heart connections during cardiac arrest for early stage prognosis and treatments to improve outcome

Spreading depolarization (SD) is a massive release of ions and energy that travels across the brain surface and is detectable using electrical recordings. SD is sometimes called a “brain tsunami,” alluding to the fact that they are the largest and most powerful brain waves detected. The most common causes of SD include migraine auras (sensory disturbances that can precede the headache), seizures, traumatic brain injuries (TBI), strokes, and cardiac arrest (CA) which starves the brain of oxygen. Understanding SD is important to physicians because SD can cause brain tissue to swell and release toxic chemicals that can trigger the death of neurons.

While previous investigations have looked at how SD affects brain tissue directly, we want to see if SD can also have impacts on organ systems beyond the brain. Using a rat model of CA, our lab was the first to show SD may change the rate at which blood pressure drops off as the heart becomes progressively weaker. This may not be as surprising as it appears since the heart and brain are interconnected through a variety of pathways called the autonomic nervous system, the most famous such pathway being the vagus nerve. We suspect that SD alters how the vagus nerve communicates with the heart, perhaps triggering arrhythmias (irregular heart rhythms) that can be detected by monitoring the electrical activity of the heart. Other researchers have found that stimulating the vagus nerve with electrodes can make it harder for SD to happen in the brain, but no one has yet done experiments to see if stopping SDs can also stop arrhythmias in the heart.

Our lab specializes in a rat model of CA and cardiopulmonary resuscitation (CPR), and we want to be the first to test the hypothesis that SD induces arrhythmias due to vagus nerve signaling. We induce CA in a rat by stopping its air supply (done as humanely as possible and approved by veterinarians), which mimics choking, drowning, or drug overdoses in humans. We then will use electrical and optical recordings of brain activity and metabolism, as well as recordings of heart activity and blood pressure. This will allow us to correlate SD events in the brain to arrhythmias in the heart by using computational algorithms to extract detailed statistics. After we establish whether SD is correlated with arrhythmias, we will experimentally block or stimulate the vagus nerve with electrodes or drugs to test this relationship between the heart and brain.

Doing these experiments in animals will tell us what to look for in human patients. In parallel to these animal experiments, we will use a database of brain recordings during CA in the hospital to see if the same signatures of SD and arrhythmia occur simultaneously in patients. Even after successful CPR, most people who have CA are left in comas or have permanent brain damage. Understanding how the brain interacts with the heart during the process of dying may be the first step to allow doctors to develop better, targeted resuscitation methods.

Click here to visit the announcement on the UCI Institute for Clinical & Translational Science website.

The Office of the Dean is pleased to announce the acceptance of Kristen M. Kelly, MD, as a fellow in the Hedwig van Ameringen Executive Leadership in Academic Medicine (ELAM) Program. Dr. Kelly is chair of the Department of Dermatology at the UCI School of Medicine,  and a professor in the Departments of Dermatology and Surgery at UCI School of Medicine. She is also a clinical researcher at the UCI Beckman Laser Institute & Medical Clinic.

ELAM is an intensive one-year program of leadership training with extensive coaching, networking and mentoring opportunities aimed at expanding the national pool of qualified women candidates for leadership in academic medicine, dentistry and public health. Dr. Kelly will participate in this one-year curriculum focused on strategic finance, organizational dynamics and personal leadership effectiveness.

Click here to learn more about Kristen Kelly, MD.