Laboratory of Cell Biology

Chief
Michael M. Gottesman, M.D.
Deputy Chief
Suresh V. Ambudkar, Ph.D.

The Laboratory of Cell Biology (LCB) studies the processing, transport, and metabolism of proteins and small molecules related to malignant transformation, metastasis, and multidrug resistance in cancer. The principal investigators of the laboratory, who are experts in molecular biology, genetics, biochemistry, structural biology, cellular regulation of cell growth and metabolism, resistance to anticancer drugs, and the physics of cell-matrix interactions, work on research projects related to those topics. The Multidrug Resistance Section studies the molecular basis of anticancer drug resistance, while the Transport Biochemistry Section investigates the biochemistry of energy-dependent transporters. Post-translational regulation of the tumor suppressor p53 and the roles of Wip1 in promoting cellular proliferation are the focus of the Chemical Immunology Section, while the DNA and Nucleoproteins Section is involved in computational and experimental studies of nucleic acid-protein interactions. The Biochemistry of Proteins Section studies the role of ATP-dependent proteolysis in multiple cellular processes. The Biophysics Section develops novel EM-based approaches to determine single molecule and multisubunit structures. The Tissue Morphodynamics Unit studies how normal and cancer cells modify their environments to promote normal differentiation and cancer cell metastasis. Finally, the Crystallography Section works on X-ray crystallography of membrane proteins and protein complexes.

LCB also includes three Cores, one involved in 3D electron microscopy, one in molecular modeling, and one in characterization of post-transcriptional protein processing. Joint journal clubs and data presentations among some sections, and laboratory-wide research seminars facilitate the sharing of expertise and help to foster collaborations among members. LCB investigators have contributed to characterizing important cellular processes involved in the development, prevention and/or treatment of cancer. For example, the multidrug transporter, an energy-dependent efflux pump (ABC transporter) for many different cytotoxic chemotherapeutic drugs that contributes to drug resistance of approximately half of all human cancers, was cloned and characterized in the laboratory and new ABC transporters and other mechanisms involved in drug resistance have been characterized. Two bacterial ATP-dependent proteases, LON and CLP, which have mammalian mitochondrial homologs, have been characterized and shown to share structural and catalytic features with mammalian proteosomes that are responsible for energy-dependent regulation of proteolysis in mammalian cells. The alternate metabolic pathways involved in melanin biosynthesis, a natural pigment that protects against UV-related DNA damage, have been defined. The structural requirements for binding of peptides to class I and class II major histocompatibility complex (MHC) molecules have been determined, and this information is being applied to the production of anticancer vaccines. The observation that Wip1 is overexpressed in several human cancers motivates the development of specific inhibitors that selectively target its activity. Structural analysis of membrane proteins and protein complexes involved in energy generation, cancer, and HIV has been advanced using computational, X-ray and high-resolution EM approaches.

Position Contact Name Contact E-mail Contact Phone Research Area Keywords Number of Positions
Physicist/Bioengineering Postdoctoral Fellow Kandice Tanner

kandice.tanner@nih.gov

mechanobiology, biophysics, rheology, optical trap

1
Postdoctoral Fellow Dr. Kandice Tanner

kandice.tanner@nih.gov

301-435-6296

tumor microenvironment, genetic analysis, in vivo imaging

1

Symposium

Celebrating 30 Years of Research on Multidrug Resistance and ABC Transporters 

September 22-23, 2016, NIH Campus, Building 35, Room 620-630

The discovery and characterization of P-glycoprotein as a mechanism of multidrug resistance is widely accepted as a seminal contribution to the ongoing effort to end death and alleviate suffering caused by cancer. In honor of the 30th anniversary of the cloning of the human MDR1 (ABCB1) gene, we are planning a day-and-a-half scientific symposium on the NIH campus in Bethesda, Maryland, on September 22 and 23, 2016.  This event will include current and former members of the MDR group in the Laboratory of Cell Biology, as well as collaborators and colleagues in the field.  The first day of scientific talks and discussions will be followed by a dinner in celebration of this anniversary. 

If you would like to attend the symposium, please contact George Leiman for a registration form:  leimang@mail.nih.gov

All LCB seminars are held at 2:15 in Building 37, Room 2041 unless otherwise noted

May

3       Michael Dean, Laboratory Of Translational Genomics, NCI (guest of Michael Gottesman)

The Vertebrate ABC Transporter Genes: Evolution, Function and Disease

10     Tenure-track Updates-
Yamini Dalal, Laboratory of Receptor Biology and Gene Expression, NCI Building 41

Head, Chromatin Structure and Epigenetic Mechanisms Group

 Alexander Kelly, Laboratory of Biochemistry and Molecular Biology, NCI Building 37

Head, Chromosome Dynamics and Genome Stability Section

17
24 Erin Tran, Biophysics Section, LCB
31

 

June

7  Fei Zhou, Chrystallography Section

P-glycoprotein Structures Reveal Functional Asymmetry and Principle of Substrate Polyspecificity

14 Tatiana Nikitina, DNA and Nucleoproteins Section, LCB
21 Khurts Shilagardi, Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine (guest of Michael Gottesman)

A Novel Function of ABC Transporters in Cell Fusion

28 Robert Robey, Multidrug Resistance Section, LCB

 

 

About

The Laboratory of Cell Biology (LCB) studies the processing, transport, and metabolism of proteins and small molecules related to malignant transformation, metastasis, and multidrug resistance in cancer. The principal investigators of the laboratory, who are experts in molecular biology, genetics, biochemistry, structural biology, cellular regulation of cell growth and metabolism, resistance to anticancer drugs, and the physics of cell-matrix interactions, work on research projects related to those topics. The Multidrug Resistance Section studies the molecular basis of anticancer drug resistance, while the Transport Biochemistry Section investigates the biochemistry of energy-dependent transporters. Post-translational regulation of the tumor suppressor p53 and the roles of Wip1 in promoting cellular proliferation are the focus of the Chemical Immunology Section, while the DNA and Nucleoproteins Section is involved in computational and experimental studies of nucleic acid-protein interactions. The Biochemistry of Proteins Section studies the role of ATP-dependent proteolysis in multiple cellular processes. The Biophysics Section develops novel EM-based approaches to determine single molecule and multisubunit structures. The Tissue Morphodynamics Unit studies how normal and cancer cells modify their environments to promote normal differentiation and cancer cell metastasis. Finally, the Crystallography Section works on X-ray crystallography of membrane proteins and protein complexes.

LCB also includes three Cores, one involved in 3D electron microscopy, one in molecular modeling, and one in characterization of post-transcriptional protein processing. Joint journal clubs and data presentations among some sections, and laboratory-wide research seminars facilitate the sharing of expertise and help to foster collaborations among members. LCB investigators have contributed to characterizing important cellular processes involved in the development, prevention and/or treatment of cancer. For example, the multidrug transporter, an energy-dependent efflux pump (ABC transporter) for many different cytotoxic chemotherapeutic drugs that contributes to drug resistance of approximately half of all human cancers, was cloned and characterized in the laboratory and new ABC transporters and other mechanisms involved in drug resistance have been characterized. Two bacterial ATP-dependent proteases, LON and CLP, which have mammalian mitochondrial homologs, have been characterized and shown to share structural and catalytic features with mammalian proteosomes that are responsible for energy-dependent regulation of proteolysis in mammalian cells. The alternate metabolic pathways involved in melanin biosynthesis, a natural pigment that protects against UV-related DNA damage, have been defined. The structural requirements for binding of peptides to class I and class II major histocompatibility complex (MHC) molecules have been determined, and this information is being applied to the production of anticancer vaccines. The observation that Wip1 is overexpressed in several human cancers motivates the development of specific inhibitors that selectively target its activity. Structural analysis of membrane proteins and protein complexes involved in energy generation, cancer, and HIV has been advanced using computational, X-ray and high-resolution EM approaches.

PI & Key Staff

Positions

Position Contact Name Contact E-mail Contact Phone Research Area Keywords Number of Positions
Physicist/Bioengineering Postdoctoral Fellow Kandice Tanner

kandice.tanner@nih.gov

mechanobiology, biophysics, rheology, optical trap

1
Postdoctoral Fellow Dr. Kandice Tanner

kandice.tanner@nih.gov

301-435-6296

tumor microenvironment, genetic analysis, in vivo imaging

1

Contact Info

Laboratory of Cell Biology
Center for Cancer Research
National Cancer Institute
Building 37 Room 2108
Bethesda, MD 20892-4256
Ph: 301-496-1530
Editorial and Office Assistant
Program Specialist
301-496-1530
Technical Lab Manager
301-402-0687