Alexey Terskikh Archives - Sanford Burnham Prebys
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A year in review: Our top 10 discoveries of 2019

AuthorMonica May
Date

December 4, 2019

At Sanford Burnham Prebys, we uncover the origins of disease and launch bold new strategies that lay the foundation for achieving cures. This year our scientists made significant progress—revealing new insights into how we treat some of the deadliest cancers, address neurological disorders such as Parkinson’s and amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) and more.

Read on to learn more about our top 10 discoveries of the year. To receive more frequent updates on our discoveries, subscribe to our monthly newsletter at the bottom of this page.

  1. One-two punch drug combination offers hope for pancreatic cancer therapy. Ze’ev Ronai, PhD, identified a combination of two anti-cancer compounds that shrank pancreatic tumors in mice—supporting the immediate evaluation of the drugs in a clinical trial. The study was published in Nature Cell Biology.
  2. Targeted treatment shrinks deadly pediatric brain tumors. Robert Wechsler-Reya, PhD, reported that a targeted therapy that blocks a protein called LSD1 shrank tumors in mice with a form of pediatric brain cancer known as medulloblastoma. LSD1 inhibitors are currently under evaluation in clinical trials for other cancers, which could speed their potential path to children. The study was published in Nature Communications.
  3. Epigenetic change causes fruit fly babies to inherit diet-induced heart disease. Rolf Bodmer, PhD, showed that reversing an epigenetic modification or over-expressing two genes protected fruit fly children and grandchildren from the negative heart effects of their parents’ fatty diet. These findings help explain how obesity-related heart failure is inherited and uncover potential targets for treatment. The study was published in Nature Communications.
  4. Amyotrophic lateral sclerosis (ALS) research reveals new treatment approach. Huaxi Xu, PhD, extended the survival of mice with ALS-like symptoms by elevating levels of a protein called membralin using a gene therapy approach. The study was published in the Journal of Clinical Investigations.
  5. How prostate cancer becomes treatment resistant. Jorge Moscat, PhD, and Maria Diaz-Meco, PhD, identified how prostate cancer transforms into an aggressive, treatment-resistant subtype called neuroendocrine prostate cancer (NEPC) following treatment with anti-androgen therapy. Their findings uncover new therapeutic avenues that could prevent this transformation from occurring and reveal that an FDA-approved drug holds promise as an NEPC treatment. The study was published in Cancer Cell.
  6. Boosting muscle stem cells to treat muscular dystrophy and aging muscles. Alessandra Sacco, PhD, uncovered a molecular signaling pathway that regulates how muscle stem cells decide whether to self-renew or differentiate—an insight that could lead to muscle-boosting therapeutics for muscular dystrophies or age-related muscle decline. The study was published in Nature Communications.
  7. Functional hair follicles grown from stem cells. Alexey Terskikh, PhD, created natural-looking hair that grows through the skin using human induced pluripotent stem cells (iPSCs), a major scientific achievement that could revolutionize the hair growth industry. Stemson Therapeutics has licensed the technology.
  8. Potential targeted treatment for acute myeloid leukemia identified. Ani Deshpande, PhD, showed that a protein called BMI1 is a promising drug target for an AML subtype in which two normally separate genes fuse together. The findings, published in Experimental Hematology, provide a rationale for evaluating a BMl1-inhibiting drug that is currently in clinical development as a potential treatment for this subtype.
  9. Antimicrobial protein implicated in Parkinson’s disease. An immune system protein that usually protects the body from pathogens is abnormally produced in the brain during Parkinson’s disease, Wanda Reynolds, PhD, reported in Free Radical Biology & Medicine. The discovery indicates that developing a drug that blocks this protein, called myeloperoxidase (MPO), may help people with Parkinson’s disease.
  10. Digestion-aiding herbs alter gut microbiome. Scott Peterson, PhD, found that four herbs—turmeric, ginger, long pepper and black pepper—promoted strong shifts in the gut bacteria that are known to regulate metabolism, providing insights that could help us protect our health. The study was published in Evidence-Based Complementary and Alternative Medicine.
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SBP’s Alexey Terskikh advances hair growth research

AuthorMonica May
Date

August 16, 2018

Three years ago, Alexey Terskikh, PhD, associate professor in Sanford Burnham Prebys Medical Discovery Institute’s (SBP’s) Development, Aging and Regeneration Program, published a groundbreaking study showing that stem cells could be used to grow hair.

This discovery could help more than 80 million men, women and children in the United States experiencing hair loss. Across cultures, personal identity is connected with hair. As a result, hair loss often affects emotional well-being and self-esteem. There is clear interest in the technology: Our 2015 story on this finding remains our blog’s most-read article. 

Since then, Terskikh and his team have been working hard to advance this technology. We caught up with Terskikh to learn about his progress—and how far away the research remains from human studies. 

Alexey Terskikh
     Alexey Terskikh, PhD

Could you fill us in on your work since 2015?

For the past three years, my team and I have been working to overcome several obstacles to the technology’s real-world use. We’ve made progress on multiple fronts, summarized below:

Generating unlimited cells 
Instead of embryonic stem cells, which are difficult to obtain, our method now uses induced pluripotent stem cells (iPSC), which are derived from a simple blood draw or skin sample. iPSCs allow us to create an unlimited supply of cells to grow hair. Not having enough hair is one reason current transplants don’t work, so this is a critical advance.

Creating a natural look
Hair actually grows in a specific direction, so it’s important to control the orientation of hair growth to achieve a natural look. Your hair stylist is familiar with this!

We’ve found a solution—3D biodegradable scaffolds—and partnered with leading scientists in the field to advance our project. The scaffold allows us to control the number of cells transplanted, their direction and where they are placed.

Helping the transplant “take”
The scaffold has a second job of helping seed hair follicles. Skin is a good barrier—that’s its job—so we needed something to help the transplant “take.” The scaffold provides the “soil” from which the hair can grow. 

Hair-generating cells in mouse skin
Hair-inducing human cells (red)
generated from iPSC present within hair
follicles grown in mouse skin. 

I understand you have formed a company based on this research. Can you tell us more? 

Yes, we have formed a company this year and assembled a great team with the expertise needed to move the technology forward. These experts include hair transplantation specialists, experienced entrepreneurs and experts in manufacturing cells at large scale (not a trivial endeavor). 

While hair loss affects people’s self-esteem and self-image, it isn’t life threatening, so it’s not a top priority for many funding agencies. Forming a company gives us a vehicle for raising capital to advance this technology.

Do you know how the stem cell–generated hair will look? Can you control hair color? 
We hope that stem cell–generated hair will look exactly as the original hairs that have been lost. Of course, it will take some time to grow a “perfect” hair, but we believe this should be possible in the long run.

Has anything surprised you during this process? 
I expected to hear from young and older men, but I was surprised by the number of women who reached out to express interest in our research. I received about an equal number of emails from women. Pregnancy, menopause and ovarian conditions may all cause hair loss for women. 

Most heartbreaking were emails from parents of children with alopecia, a condition where a child cannot grow hair. As you can imagine, hair loss at such a young age can affect relationship formation and self-image. All these emails continue to motivate me to keep advancing this research as quickly as possible.

What work needs to be done before you can test this on humans? How far away are we from this product being used on humans?

The good news is that we’ve resolved the biological mystery of hair growth using stem cells. Now, it is mostly an engineering exercise: how to get robust and properly oriented hair growth. 

Before we can discuss human studies with the U.S. Food and Drug Administration (FDA), we need to complete safety and tumorigenicity tests in mice. We are performing these tests very soon. 

Provided we have the proper funding, we expect it will take two years before we can start discussions with the FDA.

Assuming all goes as planned and the FDA approves a first-in-human study, will everyone be eligible for the trial? 

At that point we will work very closely with clinical experts in the field to determine which individuals are most likely to benefit from this research and should be involved in the trial. 

How did you first get started on this research? 

That’s actually a funny story. My father—who is a scientist—wanted to stay more in touch, so we decided to do a joint project. I was researching stem cells, and he was researching skin follicles, so we ended up here! If you look at the paper, you’ll see two authors who have the same last name—him and me. 

Interested in keeping up with SBP’s latest discoveries, upcoming events and more? Subscribe to our monthly newsletter, Discoveries.

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Off-the-shelf drugs could help manage Zika

AuthorSusan Gammon
Date

February 2, 2018

The Zika virus has been relatively quiet lately, but that doesn’t mean the danger is over. Zika can come roaring back at any time, generating severe birth defects and other health issues.

That makes it a race against time. Can scientists and clinicians develop effective Zika therapies before the virus rebounds? The normal drug discovery process takes 10 to 20 years, and we clearly don’t have that much time. But there’s another option: Retasking drugs that have already been approved for other conditions could dramatically shorten the approval process.

“It’s important to find drugs that are immediately available that you can put in the pipeline to treat Zika,” says Alexey Terskikh, PhD, associate professor at SBP.

A recent paper from Terskikh and UC San Diego’s Alysson Muotri, PhD, highlighted this possible solution. Published in Nature Scientific Reports, the study showed sofosbuvir (Sovaldi), a drug made by Gilead to treat hepatitis C, could also be effective against Zika.

Sovaldi neutralizes an RNA polymerase – an enzyme that transcribes RNA from DNA. By disrupting this pathway, Sovaldi prevents hepatitis C from replicating. Because Zika has a similar RNA polymerase, a number of labs have been looking at Sovaldi’s possible impact on the virus. The collaborative work conducted by the Terskikh and Muotri labs showed the drug decreased viral levels, reduced neural cell death and limited the amount of virus transmitted to babies.

This work reinforces a previous study, published in Nature Scientific Reports last November, that shows the anti-malaria drug chloroquine reduces Zika transmission between mothers and babies in a mouse model.

Chloroquine offers a number of advantages. It’s inexpensive, generally available in the countries most affected by Zika and poses no risk to pregnancy.

“Chloroquine has been tested in pregnant women for the past 50 years in high doses and has been found safe,” says Terskikh.

The researchers believe a drug cocktail, including Sovaldi, chloroquine and perhaps other drugs, could be effective against Zika.

“It’s possible we could use both drugs,” says Terskikh. “We are working on a grant proposal to test different combinations. Most antiviral therapies rely on a cocktail—for example many HIV treatments are a mix of three or four drugs.”

But most importantly for Zika, these drugs are already being made in significant quantities and, should another epidemic arise, could potentially help stem the outbreak and protect vulnerable people.

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Zika virus may affect adult brain cells in those with immune deficiencies

AuthorJessica Moore
Date

August 19, 2016

Concerns over the Zika virus have focused on pregnant women due to mounting evidence that it causes brain abnormalities in developing fetuses. However, new research to which Alexey Terskikh, PhD, associate professor in the Development, Aging, and Regeneration Program, contributed, provides tentative evidence that certain adult brain cells may be vulnerable to infection as well. These cells replace lost or damaged neurons throughout adulthood, and are critical to learning and memory.

 

“We examined whether the Zika virus can get into the adult brain by infecting mice. Since normal adult mice are resistant to Zika, we used special mice that lack a major antiviral response,” said Terskikh. “We found that in these mice the virus infects neural progenitor cells (NPCs). This suggests that people who have been infected with Zika might, in the long term, develop neurological symptoms such as memory or mood problems—and people with weakened immune systems would be especially vulnerable.”

The investigation, published in Cell Stem Cell, was co-led by Joseph Gleeson, MD, adjunct professor at Rockefeller University, and Sujan Shresta, PhD, professor at the La Jolla Institute of Allergy and Immunology. Terskikh’s lab performed the experiments, which he helped design, in parallel with the other teams.

In adults, NPCs are found in two small regions of the brain. Infection correlated with evidence of cell death and reduced generation of new neurons in these regions. Similar deficits have been linked to cognitive decline and depression.

Since Zika infections in healthy humans lead to much lower viral counts than those in the mice in the study, whether the virus enters the brain in typical cases remains unclear.

“The majority of adults who are infected with Zika rarely show detectable symptoms,” said Shresta. “Its effect on the adult brain may be subtle, and now we know what to look for.”

To better understand the effects of Zika on normal adult brains, Terskikh’s lab is now using a different mouse line with a dampened, rather than absent, antiviral response.

The paper is available online here.

This post is based in part on a press release from Rockefeller University and the La Jolla Institute for Allergy and Immunology.

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SBP’s 37th Annual Symposium: Aging and Regeneration

Authorsgammon
Date

November 3, 2015

On Friday, October 30, more 350 people came to SBP’s 37th Annual Symposium to hear leading scientists present their latest research on aging and regeneration.  The presenters, listed here, provided valuable insight into the latest studies on what causes aging, and strategies to repair injuries, prolong life, and prevent diseases.  The event was hosted by (from left to right): Rolf Bodmer, PhD, Malene Hansen, PhD, (in bee costume for Halloween) Alexey Terskikh, PhD

 

organizers-symposium-beaker

Many congratulations to Esther Minotti for successfully organizing the event!

symposium-photo-beaker

And many thanks to the Glenn Foundation for Medical Research for their support.

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Discovery of new role of SOX2 protein sheds light on neurogenesis in the adult brain

Authorsgammon
Date

April 21, 2015

 

Newborn neurons generated from neural progenitor cells in a brain region called the hippocampus play an important role in learning and memory in adults. However, the molecular mechanisms that control this neurogenesis process have not been fully understood. Sanford-Burnham researchers recently shed new light on this question by discovering a key role of a protein called SOX2 in neuronal development. As reported online in Proceedings of the National Academy of Sciences, SOX2 promotes the activation of genes involved in differentiation, enabling neural progenitor cells to turn into mature neurons in the brains of adult mice. Continue reading “Discovery of new role of SOX2 protein sheds light on neurogenesis in the adult brain”

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Stem cells grow new hair – Arabic translation

Authorsgammon
Date

January 27, 2015

“دراسة جديدة لنمو الشعر”

في دراسة جديدة، إستخدم الباحثون في معهد سان- برونهام الخلايا الجذعه المحفزة1 في جسم الإنسان لتعمل على توليد ونمو الشعر الجديد. وتمثل هذه الدراسة خطوة أولى نحو تطوير علاج عن طريق الخلايا الجذعية للأشخاص الذين يعانون من مشكلة فغداً الشعر “الصلع” .في الولايات المتحدة وحدها، يعاني أكثر من 40 مليون رجل و 21 مليون إمرأة من مشكلة فقدان الشعر، ولقد تم نشر هذا البحث على الإنترنت في بلوس وان. 

تبرعكم سوف يصنع الفرق الرجاء التبرع للدكتور ألكسي للمضي قدما في هذا الإنجاز.

“لقد قمنا بتطوير طريقة إستخدام الخلايا الجذعية المحفزه لخلق خلية جديدة قادرة على بدء نمو الشعر عند الإنسان”. و قال ألكسي ترسكي و هو دكتور أستاذ مشارك في معهد التنميه، والشيخوخة و برامج التجديد ” طريقة إستعمال الخلايا الجذعية توفر مصدرا غير محدود من الخلايا من المريض لعملية زراعة الشعر وهي ليست محدودة كالطرق المستعملة حالياً عن طريق إستخدام ونزع بصيلات الشعر المتواجدة من الأصل. طور فريق البحث نظام يعمل على تمايز الخلايا الجذعية المحفزة عند الإنسان لتصبح وتتحول إلى خلايا جلدية حليمة. هذه الخلايا الجلدية تعد خلايا فريده من نوعها وتعمل على تنظيم تشكيل بصيلات الشعر و دورة نموه. هذه الخلايا الجلدية لا تعد مناسبة لنمو الشعر من تلقاء نفسها لأنها لا تتوفر بالكميات المطلوبة وتفقد قدرتها بسرعة على حث تشكيل بصيلات الشعر بدون عمله التمايز مع الخلايا الجذعية. 

عند البالغين، هذه الخلايا الجلدية يمكن تضخيمها خارج الجسم، وأنها سرعان ما تفقد خصائصها في عملية تحفيز الشعر”.يقول الدكتور ألكسي “لقد قمنا بإبتكار نظام يعمل لدفع الخليا الجذعية المحفزه عند الإنسان لتتمايز أو تتحول إلى خلايا جلدية حليمة، وقد أكد نجاح التجربة حيث أكد على قدرة هذه الخلايا على حث نمو الشعر عند زرعها عند الفئران”. خطوتنا التاليه هي زراعة الخلايا الجذعية المحفزة عند الإنسان مرة أخرى إلى جسم الإنسان، و نحن حالياً نسعى إلى شركات لتنفيذ الخطوة الأخيرة”. 

شاهد المزيد على الرابط 
 

تبرع

 

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Stem cells grow new hair – Chinese translation

Authorsgammon
Date

January 27, 2015

用干细胞促生毛发

在一项新的研究中,桑福德 – 伯纳姆的研究人员利用人类多能干细胞促生出新的头发。该研究代表了以细胞为基础的治疗人类脱发的第一步。仅在美国,就有超过4000万男性和21万女性有着脱发困扰。这项研究在PLOS ONE在线发表。 

您的资助很重要。请帮助捷列克博士继续这项研究!

“我们已开发出一种使用人类多能干细胞的方法,来创造能够引发人体毛发生长的新的细胞。该方法相对于目前那种依赖于将毛囊从头的一个部位移植到另一个部位的方法有显着的改善,”阿列克谢-捷列克博士说。身为桑福德 – 伯纳姆的研究院发展、老化、再生项目副教授的捷列克博士还指出:“我们的干细胞的方法为移植提供了无限多的来自病人的细胞源,而不受现有的毛囊的限制。” 

该研究小组开发了促使多能干细胞成为真皮毛乳头细胞的程序。真皮毛乳头细胞是一种调节毛囊形成和生长周期的独特细胞。如果只靠本身的话,毛乳头细胞并不适合于头发移植,原因是:它们的采集量不够,而且在采集后便很快失去其诱导毛囊形成的能力。 

“对成人来说,真皮毛乳头细胞不易在体外扩增,而且会很快失去它们的生发功能,”捷列克博士说。他还说:“我们开发了一个驱动人类多能干细胞分化为毛乳头细胞的程序,并通过移植到小鼠身上的实验证实了它们的生发能力。” 

“我们的下一个步骤是将那些由人类多能干细胞衍生出的人类真皮毛乳头细胞移植回人体。目前,我们正在寻求合作伙伴来实现这最后一步。” 

更多信息见 

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Using stem cells to grow new hair

Authorsgammon
Date

January 27, 2015

In a new study, Sanford-Burnham researchers have used human pluripotent stem cells to generate new hair. The study represents the first step toward the development of a cell-based treatment for people with hair loss. In the United States alone, more than 40 million men and 21 million women are affected by hair loss. The research was published online in PLOS ONE.

“We have developed a method using human pluripotent stem cells to create new cells capable of initiating human hair growth. The method is a marked improvement over current methods that rely on transplanting existing hair follicles from one part of the head to another,” said Alexey Terskikh, PhD, associate professor in the Development, Aging, and Regeneration Program. “Our stem cell method provides an unlimited source of cells from the patient for transplantation and isn’t limited by the availability of existing hair follicles.”

The research team developed a protocol that coaxed human pluripotent stem cells to become dermal papilla cells. They are a unique population of cells that regulate hair-follicle formation and growth cycle. Human dermal papilla cells on their own are not suitable for hair transplants because they cannot be obtained in necessary amounts and rapidly lose their ability to induce hair-follicle formation in culture.

“In adults, dermal papilla cells cannot be readily amplified outside of the body and they quickly lose their hair-inducing properties,” said Terskikh. “We developed a protocol to drive human pluripotent stem cells to differentiate into dermal papilla cells and confirmed their ability to induce hair growth when transplanted into mice.”

“Our next step is to transplant human dermal papilla cells derived from human pluripotent stem cells back into human subjects,” said Terskikh. “We are currently seeking partnerships to implement this final step.”

View translations of this story

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