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 3^rd floor, room 305
335 Sutherland Dr
Pittsburgh, PA, 15261

Email: sib51@pitt.edu

Website link: https://brixiuslab.org/

Structure and function of cellular machinery in human parasites

My lab is dedicated to the experimental and computational application of cryo-ET for structural determination of biological macromolecules or biological machinery in single-celled parasites that cause important human diseases. I am particularly interested in understanding the molecules transportation, organelle biogenesis and their regulations in the invasion process of the malaria parasites (or related apicomplexan parasites) and the migration of Trypanosoma brucei that causes African sleeping sickness in humans and Nagano in cattle. Our research is to visualize the organization of cellular structures and their coordination in 3D spatial organization through a multi-scale imaging platform ranging from microns to sub-nanometers, to elucidate the molecular and structure functions that drive cell migration or invasion. Crucially, the novel cryo-ET analysis developed will also broadly enable the study of molecular machines in other complex biological contexts.

Education

B.S. 2008, Wuhan University, Wuhan, China
Ph.D. 2014, National University of Singapore, Singapore

Postdoctoral Training

2014-2016, Mechanobiology Institute, Singapore
2016-2017, Baylor College of Medicine, Houston, United States
2017-2021, Stanford University, Stanford, United States

Stella Sun
Department of Structural Biology
University of Pittsburgh
2050 Biomedical Science Tower 3
3501 5th Ave.
Pittsburgh, PA 15260

Phone: (412) 648-9959
Fax: (412) 648-9008

E-mail: stellasun@pitt.edu

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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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Synthetic biology approaches to engineer immune cells.

We use synthetic biology approaches to genetically reprogram immune cells to treat disease. Immune cells are an ideal chassis for therapeutic intervention as they are involved in the prevention or pathology of nearly every major disease, they can be genetically manipulated, and they have the capability of migrating to and affecting most locations in the body. Our major scientific goal is to overcome current barriers to successful adoptive T cell therapy, especially for solid tumors, including immune inhibitory signals of the disease micro-environment, cell-intrinsic limits to T cell persistence and function, and developing new antigen targeting strategies to avoid toxicities and cancer relapse. One key technology that we are developing is “universal” cell receptor systems that can be targeted to any cell surface antigen of interest by co-administered antibody adaptors - allowing the same engineered T cells to be used to target multiple antigens in a patient or across patients. To further enhance universal receptor specificity, we are creating conditional ON and OFF-switch adaptor molecules. Another major focus of the lab is on re-wiring immune cell signaling pathways to respond to novel inputs and the engineering of artificial cell-cell communication. Our standard experimental system for developing these technologies is viral engineering of primary human T cells followed by functional characterization in vitro by flow cytometry and live cell high-content fluorescence imaging and in vivo testing in pre-clinical humanized tumor xenograft mouse models.

Education

Sc.B.  2007, Brown University
Ph.D.  2013, Harvard University

Postdoctoral Training

2013-2019, University of Pittsburgh

Jason Lohmueller
Department of Surgery
Division of Surgical Oncology
University of Pittsburgh
Hillman Cancer Research Pavilion, Suite 1.4
5117 Centre Avenue
Pittsburgh, PA 15213

E-mail: jasonloh@pitt.edu

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