Author: Diyala Shihadih

DC Research Retreat 2019

Diyala Shihadih Uncategorized

Diabetes and Obesity Research Retreat

On behalf of the UCSF Diabetes Center, the UCSF NORC, and the UCSF DRC, we want to thank you for attending the 2019 DC Retreat. With over 150 attendees from 5 institutions, it was again a huge success. We hope the retreat served its purpose of enhancing your research and facilitate new collaborations. A special thanks to all the speakers of the retreat and congratulations again to all the winners of this year’s poster session: 1. Karlton Larson (Ryan Lab, UC Davis)2. Joseph Hendricks (Olzmann Lab, UC Berkeley)3. Jessica Chavez (Hebrok Lab, UCSF)4. Zewen (Owen) Jiang (Svensson Lab, Stanford)

Stahl Lab Alumnus

Diyala Shihadih Lab News

Garrett Dempsey, PhD

Hola mi nombre es Garrett. Originally from Illinois I moved to San Diego to attend UCSD. Now at UC Berkeley in the lab of Andreas Stahl I am researching the role of tension in brown and beige adipose tissue development and function. Outside the lab you can catch me running, cooking, writing, and attempting to learn Spanish.

Also, I write for FoundMyFitness! Follow their page!

Education and Research

UC Berkeley, PhD Candidate, 2016-2022

Metacrine Inc, Research Associate, Nov 2015- June 2016

Receptos Inc., Associate Scientist, Feb 2015-Nov 2015

University of San Diego, Undergraduate, 2011-2015

Diyala Shihadih, PhD

I’m a PhD candidate in Metabolic Biology. I grew up in the bay area and earned my bachelor’s degree in Biochemistry and Molecular Biology at UC Davis. Currently, I am researching how lipid transport and metabolism are altered in disease states such as cancer and how these altered functions can be therapeutic targets.

Education and Research

University of California, Berkeley; PhD candidate; 2015-2022

University of California, Davis; Undergraduate 2011-2015

Awards and Fellowships

UC Berkeley Chancellor’s Fellowship recipient

2018 Outstanding Graduate Student Instructor

You can also find me on ResearchGate.

Peter-James H. Zushin, PhD

Biological generalist turned metabolic biologist that is currently learning bioengineering techniques to further investigate the thermogenic adipose tissue niche in vivo. Since coming to the Stahl lab I have been involved in our CoQ, Fat-on-a-chip, and hyaluronic acid-based hydrogel for beige adipose tissue formation projects. My interests lie at the intersection of evolution, tissue development, and bioengineering techniques that can help investigate those topics!

Education and Research

UC Berkeley; Graduate Student (Ph.D); 2015-2022

Boston University; Graduate Student (M.A.); 2009-2012

University of Akron; Graduate Student (M.S.); 2006-2009

University of Akron; Undergraduate; 2001-2005

Awards and Fellowships

2018, Ruth L. Kirschstein NRSA Predoctoral Fellowship, NIH (NIBIB)

You can also find me on Research Gate.

Ching-Fang Chang, PhD

I see myself as a multidisciplinary biomedical biologist focusing on energy metabolism and stem cell biology. My goal is to find a practical intervention to effectively combat obesity and its associated metabolic disorders.

Education and Research

University of California, Berkeley; Postdoc; July 2014-2022

 

 

 

Fatty Acid Transport Proteins (FATP)

Diyala Shihadih Research

Investigating the physiological role of FATP6:

Fatty acid transport proteins are an evolutionarily conserved family of six proteins that facilitate the movement of fatty acids across cellular membranes. Many of these proteins are expressed in metabolic tissues and have a role in disease pathology and progression. We created a conditional-potential knockout mouse for fatty acid transport protein 6 (FATP6), a member of the family that has not been thoroughly studied. We are specifically interested in the biochemical activity of FATP6 in vivo and its function in cardiac tissue and reproductive organs, including the placenta.

Targeting cardiac fatty acid uptake:

Nearly half of diabetic patients experience cardiac dysfunction. Impaired left ventricular function in the absence of overt cardiovascular disease or hypertension results in a condition called diabetic cardiomyopathy. In response to elevated serum fatty acids and reduced glucose availability, hearts increase fatty acid utilization, leading to cardiac inefficiency and lipotoxicity. We hypothesize that targeting cardiac fatty acid transporters such as FATP6 will reduce cellular fatty acid uptake and therefore protect hearts from diabetic cardiomyopathy. We are currently working to create a mouse model of diabetic cardiomyopathy in which we can analyze the effects of genetic deletion of cardiac fatty acid transporters.

Targeting hepatic fatty acid uptake in a cancer model: 

Monitoring fatty acid fluxes in liver through novel in vivo assays using fluorescence labeled fatty acid and bioluminescence imaging method. Using theses methods, we identified deoxycholic acid (DCA), a natural secondary bile acid, as the most potent inhibitor of the liver-specific fatty acid transport protein 5 (FATP5). DCA were able to inhibit LCFA uptake by primary hepatocytes in a FATP5-dependent manner. We are now doing research in the inhibition mechanism of DCA on LCFA uptake through FATP5 and the effects on the survival of the liver cancer intrahepatic cholangiocarcinoma.

CoQ Transport and Thermogenesis

Diyala Shihadih Research

Classical brown adipose tissue (BAT) is a unique type of adipose tissue that is composed of adipocytes with multilocular lipid droplets and a large amount of mitochondria, making it a highly metabolically active organ that is responsible for nonshivering thermogenesis both in neonate and adult humans. Brown adipocytes possess an unparalleled ability to generate heat due to the dissociation of electron transport chain respiration from ATP production through uncoupling protein 1 (UCP1). Brown adipocyte mitochondria also display an elevated capacity for substrate utilization. A major source of substrate is the β-oxidation of long chain fatty acids (LCFA), which can be taken up from the circulation via fatty acid transport proteins (FATPs) or can be generated from endocytosed lipoproteins through a process mediated in part by the scavenger receptors. The scavenger receptor (SR) family of transmembrane glycoproteins mediates the binding and uptake of a broad range of ligands in a variety of tissues. A defining member of the SR-B receptors is CD36, which has been shown to be required in a variety of tissues for the uptake of several hydrophobic molecules, including LCFA and the carotenoid lycopene. More recently, it was demonstrated that CD36 is required for the endocytosis of lipoproteins by both macrophages and BAT.

The lipid coenzyme Q (CoQ; also known as ubiquinone) is an essential component of the mitochondrial electron transport chain. Low CoQ levels are associated with cardiomyopathies, aging, and statin-induced myopathies. There are also several genetic mutations directly affecting proteins involved in the synthesis of CoQ, resulting in primary CoQ deficiencies. Therefore, increasing CoQ levels could be therapeutically beneficial for a variety of metabolic diseases. Many tissues endogenously synthesize CoQ, and the contribution of dietary CoQ is thought to be comparatively small. However, exogenous uptake of CoQ from the circulation can be significant in situations where CoQ levels are already low, such as in genetic deficiencies, myopathies, and aging. Exactly how tissues take up CoQ and which tissues primarily depend on exogenous CoQ has not been well studied, posing a considerable challenge to the therapeutic use of CoQ in metabolic diseases, aging, and mitochondrial function. We have identified BAT as a major destination for exogenous CoQ, and that this uptake is dependent on CD36. We are currently examining the precise mechanism of CoQ uptake by CD36, the synthesis rate of CoQ in BAT lacking CD36, and the effect of exogenous CoQ on BAT function as a possible therapy for metabolic diseases.

Matrix Assisted Transplantation of Functional Brown Adipose-like Tissue

Diyala Shihadih Research

Discovering clinically relevant tactics to balance energy homeostasis and combat metabolic disorders such as obesity and diabetes is of the upmost importance. Brown adipose tissue (BAT) is a thermogenic organ that consumes energy substrates to generate heat through the mitochondrial uncoupling protein-1 (UCP1). The recent discovery that adult humans possess functional BAT and activating BAT can increase its uptake of circulating glucose and fatty acids suggests its potential therapeutic application on controlling glucose homeostasis and energy metabolism.

To study BAT, we have developed a novel method to differentiate and support the implantation of brown adipose-like fat, or beige fat. We employ an innovative Matrix-assisted Cell Transplantation (MACT) system to support the differentiation of both human and mouse pluripotent stem cells and adipose-derived mesenchymal stem cells into functional BAT, or beige adipose tissue.  The establishment of the human BAT-MACT system allows us to investigate the roles of extracellular microenvironments to support human BAT formation and maintain its function, metabolic characterization of human BAT and its effects on energy metabolism, mechanisms of human BAT expansion and maintenance, and screening pharmaceutical activators of human BAT.

We have now deployed this system in vivo and found that our Beige Adipose Tissue Matrix Assisted Cellular Implant (BAT-MACT) was able to metabolically augment the recipient. BAT-MACT recipients demonstrated elevated metabolism, improved glucose homeostasis, elevated core body temperature during cold challenges, and reduced weight gains on high fat diets. This system was developed with clinical application in mind, and thus employs materials and cell sources that will translate directly into therapeutic use to combat metabolic disorders.