Newly Discovered Genes Could Change Vitiligo Treatment

 

A recent study has revealed 135 previously unknown genes that play important roles in regulating melanin production in humans—and that could lead to melanin-modifying drugs for vitiligo and other pigmentation diseases.

The research team was led by Vivek Bajpai, assistant professor in the School of Sustainable Chemical, Biological and Materials Engineering at the University of Oklahoma, with collaborators from Stanford University, where Bajpai did postdoctoral work.

Melanin synthesis is compartmentalized within the melanosome, in specialized pigment cells (melanocytes). The synthesis of melanin within the melanosomes varies, which is why human skin, hair, and eye color vary. Pigmentation-related diseases are associated with disruptions in melanogenesis.

Melanin’s particular physicochemical properties, such as high refractive index, determine its optical properties, the researchers wrote in their article, published in Science on Aug. 11. “We reasoned that an accumulation of melanin within melanosomes would change melanocytes’ light-scattering properties.”

Bajpai developed a novel method to detect and quantify the melanin-producing activity of melanocytes: Passing light through the melanocytes, he could record whether the light was absorbed or scattered by the melanin. “If there are a lot of melanin-producing melanosomes,” he said in a University of Oklahoma press release, “the light will scatter much more than in cells with little melanin.”

The team measured light scattering through flow cytometry, capturing “dynamic shifts” in melanin levels within melanosomes. They used CRISPR-Cas9 technology to genetically engineer cells, and conducted a genome-wide genetic screen, systematically removing more than 20,000 genes from hundreds of millions of melanocytes.

Their screen identified 169 genes, including some that were previously known and 135 new melanin-promoting genes whose deletion was associated with reduced light scattering—in other words, loss of melanin.

The melanin-promoting genes are involved in diverse biological pathways, such as transcription regulation, RNA processing, and endosomal transport, the researchers say. “Consistent with their melanin-promoting role, the expression of the majority of our screen hits is elevated in darkly pigmented, compared with lightly pigmented, human melanocytes. Our analyses revealed that select melanin-promoting genes are associated with skin color variation and show evidence of local adaptation in human populations.”

By focusing on specific previously unidentified candidates, the researchers say, “we implicated a new cargo recycling pathway in melanosome function and identified a transcription factor involved in melanosome maturation. Our work provides a rich resource for further studies of melanogenesis and its relationship with skin color variation and human diseases.”

Their findings are also meaningful to a broad swath of science beyond dermatology. Bajpai’s method of targeting melanin-producing genes could lead to prevention of fungi- and bacteria-related diseases in humans and crops.

Reference: https://www.managedhealthcareexecutive.com/view/newly-discovered-genes-could-change-vitiligo-treatment

Cilt rengiyle ilişkili 135 yeni gen tespit edildi

 

İnsanlara cilt rengini veren pigmentasyonla ilgili 135 yeni gen tanımlandı. ABD'de yapılan araştırmadaki bulguların cilt kanseri ve vitiligo tedavilerinde yeni ilaç ve yol arayışına yön vermesini bekleniyor.

News Medical Life Sciences; Oklahoma Üniversitesi'nden Vivek Bajpai ve Stanford Üniversitesi'nden araştırmacılar tarafından yapılan çalışmada, insanlara cilt rengini veren pigmentasyonla ilişkili 135 yeni gen tanımlandığını yazdı. Araştırmacılar, cilt pigmenti de olarak da tanımlanan melanin üretimini etkileyen, işlevsel olarak farklı 169 gen bulurken bunlardan 135'inin daha önce pigmentasyon ile ilişkili olmadığı tespit edildi.

Araştırmaya göre, yeni keşfedilen KLF6 ve COMMD3 isimli iki genden KLF6 isimli DNA bağlayıcı protein, insanlarda ve hayvanlarda melanin üretimi kaybına yol açarken diğer türlerde ise melanin üretiminde rol oynuyor. COMMD3 ise, melanozomların asitliğini kontrol ederek melanin sentezini düzenliyor.

Cilt kanseri araştırmalarını etkileyecek

Bajpai, çalışmayla ilgili "Melanini neyin düzenlediğini anlayarak daha açık tenli insanları melanomdan veya cilt kanserinden korumaya yardımcı olabiliriz. Bu yeni melanin genlerini hedefleyerek vitiligo ve diğer pigmentasyon hastalıkları için melanin değiştiren ilaçlar da geliştirebiliriz" açıklamasında bulundu. Araştırmacılar, bu tür melanin üreten genleri keşfederek mikroplara ve hastalıklara karşı etkili müdahaleler geliştirebilir. Araştırma, Journal Science  adlı dergide yayımlandı.

Kaynak: Gazete Oksijen

Vitiligo Clinic and Research Center at UMass Chan to coordinate $3.75 million remote clinical study

 

Researchers at the University of Massachusetts (UMass) Chan Medical School are currently embarking on a multi-million-dollar clinical study aiming to identify the biological and molecular signatures that may predispose at-risk individuals to developing vitiligo.1

The $3.75 million study is being funded by the National Institute of Allergy and Infectious Diseases and is led by John Harris, MD, PhD, chair and professor of dermatology and director of the Vitiligo Clinic & Research Center; Manuel Garber, PhD, professor of molecular medicine, a member of the Program in Bioinformatics and Integrative Biology, and director of the Bioinformatics Core at UMass Chan; and Medhi Rashigi, MD, assistant professor of dermatology.

The researchers note that after the first year of vitiligo treatment, depigmentation is likely to return in as many as 40% of patient cases. This is compounded, they say, by a scarcity of samples and data from a cohort of patients who are representative of the collective of those with the condition, despite a significant link between genetics and vitiligo.1

Study enrollment began on June 25, 2023, or World Vitiligo Day. Over the course of the next 5 years, researchers hope to enroll around 1,000 participants in the study, which will be conducted entirely remotely. It is anticipated that of these 1,000 participants, 200 will have a clinical vitiligo diagnosis, while the remainder of participants will be family members or direct blood relatives of those with vitiligo.

Because of the link between genetics and vitiligo, Harris, Garber, and Rashigi say that they anticipate between 40 to 60 of the 800 familial participants without vitiligo will develop vitiligo at some point throughout the study’s duration.

Sampling will be conducted on a semi-annual basis, with participants being asked to complete questionnaires and submit blood, saliva, and skin tissue samples every 6 months. The questionnaires will garner data related to patients’ health, diet, and overall lifestyle. Researchers will examine the samples and questionnaire outcomes to identify environmental and outside factors, disease onset and severity, antibodies, biomarkers, and subclinical signatures of disease.

“Using this information, clinical scientists can build models to predict disease onset, progression and relapse,” according to UMass Chan Medical School.1 “Information gleaned from the clinical study can also be used to inform the course of other autoimmune diseases in which the body’s immune system attacks its own cells.”

Reference: https://www.umassmed.edu/news/news-archives/2023/06/clinical-study-aims-to-identify-early-molecular-and-biological-signatures-of-vitiligo/