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Type 2 Diabetes Researcher Spotlight: Emmanouela Tsagkaraki, MD, PhD

Genome Editing for Browning Human Fat Cells as a Potential Therapy for Type 2 Diabetes and Other Metabolic Diseases

Date Posted: Thursday, February 10, 2022

emmanouela-tsagkaraki-adipose-research

Type 2 diabetes (T2D) is a major public health problem that’s quickly approaching a global epidemic. Scientists at the UMass Chan Medical School’s Diabetes Center of Excellence are using cutting-edge genome engineering technology to investigate a therapeutic approach to the disease. 

The laboratories of Michael Czech, PhD and Silvia Corvera, MD, understand the important role that adipocytes or fat cells play in diabetes development and progression. They’re exploring a cell therapy by manipulating the genome of adipocytes to increase fat burning and improve the metabolic function of the cells.

“While white adipocytes store energy in the form of fat, we know that brown adipocytes do the opposite by helping to burn energy,” said Emmanouela Tsagkaraki, MD, PhD, a postdoc in the Czech Lab.  “However, brown fat is not abundant in people with metabolic diseases such as Type 2 diabetes, so we’re editing genes to convert white fat cells into brown-like cells in an effort to enhance glucose metabolism.”

In a newly published study in Nature Communications, Dr. Tsagkaraki led a team of scientists who removed cell samples from humans, converted white adipocytes into brown-like cells in the lab, reproduced and multiplied those cells, and transplanted them into specialized mice to test the therapeutic approach. The data indicates the process enhanced and improved glucose metabolism.

CRISPR-enhanced human adipocyte browning as cell therapy for metabolic disease

Tsagkaraki E, Nicoloro SM, DeSouza T, Solivan-Rivera J, Desai A, Lifshitz LM, Shen Y, Kelly M, Guilherme A, Henriques F, Amrani N, Ibraheim R, Rodriguez TC, Luk K, Maitland S, Friedline RH, Tauer L, Hu X, Kim JK, Wolfe SA, Sontheimer EJ, Corvera S, Czech MP. Nat Commun. 2021 Nov 26;12(1):6931. doi: 10.1038/s41467-021-27190-y. PMID: 34836963

“These implanted cells could potentially provide brown-like cells to people who don’t otherwise have them, and provide beneficial systemic effects to their whole-body metabolism,” she said. “I am excited about the clinical potential.  It’s promising that CRISPR-based cell therapy could treat a wide range of diseases including diabetes.”

Department of Defense Funding Grant

The Czech and Corvera labs have been collaborating on this project, funded through the Department of Defense’s Partnering Principal Investigator Option.

In 2016, the Corvera Lab published in Nature Medicine a method they developed to generate new human fat cells, particularly beneficial beige fat, from precursor cells present in white fat. When those cells were implanted in mice with diabetes, their metabolism improved.

The Czech Lab, in collaboration with the Sontheimer and Wolfe labs, recently developed a novel way to deliver CRISPR/Cas9 ribonucleoprotein to fat cells. They degrade and disappear within hours after efficiently edit the DNA of fat cells. This method eliminates negative immune and toxic effects, making it safe for therapeutic applications.

The joint Department of Defense grant has been extended through 2024 to fund pre-clinical studies in non-human primates.

About Dr. Tsagkaraki

Dr. Tsagkaraki was born and raised on the Greek island of Crete and earned her MD and MSc degrees from the University of Crete Medical School. Her goal is to pursue medical residency and become a physician-scientist. The “Molecular Basis of Human Diseases” graduate program in Greece “bridged the gap between clinical care and molecular medicine research.”  

Drs. Czech and Corvera were visiting faculty members of her graduate program. They travel to Crete each year to give lectures and meet with students. “My major areas of interest have always been cell therapies and regenerative medicine,” said Dr. Tsagkaraki. “I never would have imagined these cutting-edge principals and approaches could be applied to the treatment of Type 2 diabetes until I attended their talks.”

Dr. Tsagkaraki joined the Czech Lab in 2017 to complete her master’s thesis and then began her PhD working on CRISPR/Cas9 genome engineering in adipocytes to improve metabolic activity and glucose homeostasis.

Adjusting to the United States was difficult at first. “Moving here at 25 years old and not knowing anybody was a challenge,” she said with a smile.  “I was excited to be working at UMass but there was a learning curve to living in a new environment. It allowed me to learn a lot about myself and people on campus were very friendly and helpful.”

Her parents instilled in her that to become a successful scientist, one must experience different places, meet many people and hear varied points of view and perspectives. They both come from Polytechnic backgrounds.  Her father is an engineer, and her mother is an architect. They raised her to understand the importance of investing in education, because “knowledge is something that cannot be taken away from you.”

Favorite Hobbies and Activities

  • Enjoys playing piano and singing
  • Performed with a choir in Greece, singing at festivals & events throughout Greece and Europe
  • Participated in math competitions growing up
  • Has traveled to most European countries and China. Looks forward to exploring the United States, India, Central America and doing more travel to learn about different cultures after the pandemic is over
  • Loves swimming & windsurfing - grew up 20 minutes from “the sea”

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The Corvera Lab is Examining How Different Body Fat Plays a Role in Type 2 Diabetes

Michael Czech and Silvia Corvera receive $2.5 million grant to advance potential therapy for type 2 diabetes

Corvera Lab Continues to Create "Good Fat" as a Potential Therapy for Type 2 Diabetes

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