Cellular, molecular, and biochemical principles of aging and age-related disease


 

We aim to understand aging and age-related diseases from the cellular, molecular, and biochemical levels. Cellular quality control systems respond to and resolve different types of cell stress and are important in maintaining our cellular homeostasis and overall health. However, these quality control systems or stress response pathways are often compromised in aging, causing various diseases. We ask whether we can solve the problem of aging by boosting cellular quality control systems. To answer this question, we are currently searching for all unknown cellular stress response mechanisms through unbiased approaches. Our goal is to combinatorically target multiple stress response pathways to maximize our resistance to cellular stress for healthy aging and for potential treatment of age-related diseases. Our recent discoveries include an essential rapid lysosomal repair pathway (the PITT pathway) in response to lysosomal damage and a conserved ion channel function of stimulator of interferon genes (STING) in non-canonical autophagy which is activated in many conditions including infection, cellular damage, senescence, or age-related diseases such as Parkinson’s and Alzheimer’s diseases. Within the next five years, we will focus on the mechanistic investigation of two processes: (1) lysosomal quality control in response to diverse cellular stress stimuli, and (2) STING-mediated non-canonical autophagy and cell death. We search for essential, unifying principles behind complex stress responses, and dissect the underlying mechanisms using multidisciplinary methods including molecular biology, biochemistry, cell biology, and genetics. Unbiased screens, molecular cloning, cell engineering, and microscopic imaging are among the major strengths of our lab. Structural analysis and functional mutagenesis are integral parts of all our projects. Lipid signaling and membrane biology are also incorporated into all directions.

 

 


Education

  • S. in Science with Honors from Nanjing University (China), 2005-2009
  • D. in Molecular and cellular Pharmacology from University of Wisconsin-Madison, 2009-2015
  • Postdoctoral training at the University of Texas Southwestern Medical Center in the laboratory of Zhijian James Chen, 2016-2019
  • Research faculty training at the University of Pittsburgh in the laboratory of Toren Finkel, 2019-2022

 




Aging Institute
100 Technology Drive, Room 457
Pittsburgh, PA 15219
Phone: 412-624-2291
Email: Jay.Tan@Pitt.edu
Phone:4122683390

Website link: jaytanlab.org

 


 

Membrane Protein Quality Control, Mitochondria, Cancer, and Neurodegenerative Diseases


 

Mitochondria are endosymbiotic organelles that serve as key hubs for apoptotic regulation, metabolism, and cellular signaling in eukaryotic cells. Over 99% of the ~1500 mitochondrial proteins are encoded in the nuclear genome and depend on specific targeting signals to direct them from the site of synthesis in the cytosol to the appropriate subcompartment. Proper mitochondrial function depends on a process called proteostasis, which ensures that functional proteins are in the right location at the right concentration at the right time. Membrane proteins present unique challenges to the proteostasis network as they must be targeted to the correct membrane and overcome substantial thermodynamic barriers to enter and exit the lipid bilayer, all while avoiding the formation of potentially toxic aggregates in the cytosol. Failures in proteostasis are associated with many neurodegenerative diseases, whereas cancer cells are acutely dependent on robust proteostasis networks to counteract the protein imbalances caused by aneuploidy and dysregulated protein synthesis.

 

Despite the clear physiological importance, our mechanistic understanding of mitochondrial proteostasis is remarkably incomplete. My lab addresses this critical knowledge gap by focusing on three questions: (1) How do quality control factors discriminate between bona fide substrates and functional proteins in a complex cellular environment, such as the lipid bilayer; (2) once a substrate is recognized, what are the downstream steps that lead to resolution of proteotoxic stress; and (3) how can we leverage the resulting mechanistic insights to develop therapeutic interventions in cancer and neurodegenerative disease? We address these questions using a combination of biochemistry, biophysics, and structural, molecular, and cell biology.

 

 


Education

  • Education: Ph.D. 2013, MIT

Postdoctoral Training

  • Postdoctoral Training: 2018, University of Chicago




Mail to:

Lab location:
Department of Cell Biology
3500 Terrace Street
S326 Biomedical Science Tower
Pittsburgh, PA 15261

Office: 412-648-7482
Lab: 412-648-9713

 

Email: Wohlever@pitt.edu

Website link: https://wohleverlab.wordpress.com/

 


 

Our research is focused on elucidating the structure function relationship of cytochrome P450 enzymes in lung cancer using biochemistry, cell biology, and X-ray protein crystallography.


 

Members of the cytochrome P450 CYP4F family belong to a group of w-hydroxylases which produce important lipid mediators in the human body. One of these lipid mediators is the molecule 20-hydroxyeicosatetraenoic acid (20-HETE) which is regulating the blood pressure and promotes the formation of new blood vessels in healthy humans. In cancer, 20-HETE promotes cell proliferation and invasion and thus, 20-HETE generating cytochrome P450 enzymes might be exciting new drug targets for cancer treatment.

We use a combination of cell biology and biochemistry to assess the role and function of CYP4F enzymes in oncogenesis and cancer progression. Moreover, we use X-ray protein crystallography to solve structures of CYP4F enzymes for directed design of selective drugs which only inhibit the target and not any of the other 56 P450s in the human body.

 

 

 


Education

  • Diploma in Molecular and Human Biology from Saarland University (Germany), 2012
  • PhD in Biochemistry from Saarland University in the laboratory of Rita Bernhardt (Germany), 2012-2016

Postdoctoral Training

  • Postdoctoral training at Saarland University (Germany) in the laboratory of Rita Bernhardt, 2016-2017
  • Postdoctoral training at the University of Michigan in the laboratory of Emily Scott, 2017-2021




Mail to:

Lab location:
School of Pharmacy Department of Pharmaceutical Sciences
Center for Pharmacogenetics
Salk Pavilion 3rd floor, room 305
335 Sutherland Dr
Pittsburgh, PA, 15261

Email: sib51@pitt.edu

Website link: https://brixiuslab.org/

 


 

We develop next generation multimodal (electrical-optical and chemical) neural interfaces.


 

Maysam Chamanzar, is the William D. and Nancy W. Strecker Associate Professor of Electrical and Computer Engineering at Carnegie Mellon University, where he is running an interdisciplinary research program at the interface of neural engineering, nanotechnology, photonics and neuroscience to design next generation multimodal neural interfaces. He is also a faculty member of the Molecular Biophysics and Structural Biology (MBSB) program, the Biomedical Engineering Department, the Carnegie Mellon Neuroscience Institute and the Center for the Neural basis of Cognition (CNBC). His lab has been working on designing novel multimodal neural interfaces to understand the neural basis of brain function and dysfunction. His lab has been developing implantable neural interfaces for recording and stimulation of brain. Additionally, his lab has pioneered a novel method of in situ light guiding and steering using ultrasound waves for non-invasive imaging.

 

 


Education

Postdoctoral Training, 2012-2015, University of California berkeley
PhD in Electrical and Computer Engineering, 2012, Georgia Institute of Technology

 




Lab: MI 166

Phone:4122683390

Email: mchamanz@andrew.cmu.edu



Website link: www.chamanzarlab.com

 


 

Molecular mechanism of amyloid fibrils in health and disease



The aim of my Lab is to understand molecular mechanisms of amyloid fibrils in health and disease. Amyloid fibrils are known for causing pathological neurodegenerative diseases such as Alzheimer’s (via Ab) or Parkinson’s (via aS), but also have specific biological functions in living organisms, functional amyloids. My research focuses on two main areas: neurodegenerative amyloid proteins and biofilm forming bacterial functional amyloids, a major cause of persistent infections and an antimicrobial resistance (AMR) target. We aim to determine atomic resolution structures and molecular dynamics information, for better understanding of amyloid formation and biofilms. This will pave the way towards future treatments against neurodegeneration, bacterial infections, and their antimicrobial resistance.

We use modern solid state NMR (ssNMR) spectroscopy to study these insoluble/non-crystalline proteins. We develop novel NMR methods to push the limits of the state of the art and apply them to understand molecular details and mechanisms of amyloid fibrils. ssNMR has made a remarkable progress in the last decade to become a high-resolution and -sensitivity method due to advances in sample preparation, hardware, novel methods such as proton-detection and hyperpolarization. These allow studies of these difficult proteins not only in vitro, but also in their complex native in vivo environment. Akbey Lab also like to combine NMR with other exciting structural biology tools.

 


Education

Undergraduate

1999-2005:       B.Sc. in Chemistry, Bilkent University, Ankara, Turkey

Graduate

2005-2008:       Ph.D. in Solid-state NMR, Max Planck Institute, Mainz, Germany

Postgraduate

2009-2015:       Leibniz Institute for Molecular Pharmacology, Berlin, Germany

2015-2018:       Aarhus University, Aarhus, Denmark
2018-2019:       Forschung Zentrum Julich, Julich, Germany
2020-2021:       Weizmann Institute of Science, Rehovot, Israel
2021:                Radboud University of Science, Nijmegen, The Netherlands




Asst. Prof. Ümit Akbey
University of Pittsburgh, Department of Structural Biology, School of Medicine
2044 Biomedical Science Tower 3
3501 5th Ave. Pittsburgh, PA, 15261, United States.
Office: +1 412 383 9896
E-mail: umitakbey@pitt.edu

Phone: (412) 383-9896
Fax: (412) 648-9008

E-mail: umitakbey@pitt.edu

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