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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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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Photo of Faculty MemberOur lab is interested in developing new tools for mapping 3D organization of biomolecules and probing biological processes in the tissue and organism.

Complex biological systems are delicate machines consist of building blocks (such as proteins, nucleic acids, lipids, and carbohydrates) that are precisely organized in the nanoscale. This presents a fundamental challenge for humanity to understand the biology and/or pathology underlying these complex systems. To gain the insight into physiological/pathological functions, one might need to map a large diversity of nanoscale building blocks, over a wide spatial scale. To tackle this challenge, we are developing a set of novel technologies that enable large scale visualization of biological samples with nanoscale precision, by physically expanding the sample rather than magnifying the light from the sample via lenses. This principle is called expansion microscopy (ExM). By combining various material engineering and chemical approaches, we are advancing ExM-based tools that may elucidate biological insights into the brain and other complex systems, such as cancer and infectious diseases.


 

Education

B.S. Chemistry, 2009, Sun Yat-sen University
PhD Chemistry, 2014, University of Alberta

Postdoctoral Training

2017, Bioengineering/Pathology, Massachusetts Institute of Technology



 

Zhao Biophotonics Laboratory
Carnegie Mellon University
202A Mellon Institute
Department of Biological Sciences
4400 Fifth Ave
Pittsburgh, PA 15213

Phone: (412) 268-8236
Fax: (412) 268-1809

E-mail: Link

Website: Link


Structure and function of transporters in neurons


 

The aim of my research is to elucidate the molecular function, architecture, and high-affinity drug binding sites of synaptic vesicle transporters in neurons by studying their function using biochemical techniques and determining their structures using single particle cryo-EM. I am particularly interested in understanding the conformational changes and mechanism associated with transporters. I have developed methods for large-scale expression, stabilization by drugs, and for the production of antibodies which recognize transporters. The use of transporter-antibody complexes is essential in order to provide mass and molecular features to assist in cryo-EM reconstructions because these transporters are small membrane proteins which are largely ensconced within membrane. Atomic structures of transporters in complex with therapeutic drugs are essential for the design of better small-molecule therapeutics with higher specificity and fewer side-effects and will also advance efforts toward understanding the function of these transporters.

 

 


Education

Aarhus University, Department of Physiology
Visiting student in lab of Dr. Jens Peter Anderson, 2010 

University of British Columbia, Department of Biochemistry and Molecular Biology
Ph.D. in lab of Dr. Rober Molday, 2007-2013

Postdoctoral Training

Oregon Health & Science University, Vollum Institute
Postdoctoral training in lab of Dr. Eric Gouaux, 2013-2020




Mail to:
Jonathan Coleman
2054 BST3
3501 Fifth Avenue
Pittsburgh, PA 15213

Phone: (412) 648-8077
Fax: (412) 648-9008

E-mail: coleman1@pitt.edu

Website link: coming soon

 


 

Structural biology, pharmacology and signaling of G protein-coupled receptors (GPCRs) and drug development

My group studies structure, pharmacology and signaling of G protein-coupled receptors (GPCRs) as important cell membrane-embedded receptors. GPCR family has over 700 members. They transduce signals from extracellular signaling molecules to intracellular effectors through conformational changes within the receptors to mediate and regulate a broad spectrum of physiological and pathological processes. GPCRs have been heavily investigated in the pharmaceutical industry, and they constitute 30-40% of current drug targets. My lab utilizes structural biology approaches including X-ray crystallography and cryo-electron microscopy (cryo-EM) and functional studies including ligand-binding assays and cellular signaling assays to explore the molecular mechanisms underlying the signal transduction of GPCRs. Currently, we focus on two groups of GPCRs, the chemotactic GPCRs involved in inflammatory diseases and the neurotransmitter GPCRs involved in neurological and psychiatric disorders. In addition, we also develop new GPCR antibodies as novel therapeutic candidates through combinatorial biology approaches such as yeast display.

 

 

 

 

 


 

Education

BS       2003, University of Science and Technology of China

PhD    2008, University of Science and Technology of China

 


Postdoctoral Training

2008-2014, Dr. Brian Kobilka's group, School of Medicine, Stanford University


 

Cheng Zhang
Department of Pharmacology and Chemical Biology
School of Medicine, University of Pittsburgh
W1311 BST
203 Lothrop St
Pittsburgh, PA15261

Website: https://www.czhanglab.org/

Phone: 412-383-8044
Email: chengzh@pitt.edu