Pamela England, PhD

Professor
Department of Pharmaceutical Chemistry
[email protected]
Phone: +1 415 502-6606
600 16th Street, Rm N512B
UCSF Box 2280
San Francisco, CA 94158
United States

Links

England Lab UCSF Profiles

Affiliations

Joint appointments

Professor, Department of Cellular and Molecular Pharmacology, School of Medicine

Education programs

Biophysics Graduate Program (BP)
Chemistry and Chemical Biology Graduate Program (CCB)
Neuroscience Graduate Program
UCSF Tetrad Graduate Program

UCSF centers, institutes, and research programs

Quantitative Biosciences Institute (QBI)

What I do

Research in the England Lab is broadly focused on developing and applying chemical probes to investigate the structure and function of signaling proteins implicated in fundamental biological processes and human diseases. Execution of these research projects typically involves a combination of synthetic chemistry, computational chemistry, structural biology, and appropriate biochemical and biological assays. Two systems currently being studied are glutamate-gated ion channels and hormone-activated nuclear receptors.

The neurotransmitter glutamate drives specific changes in the functioning of synaptic glutamate-gated ion channels. These changes modulate the strength of synaptic transmission, encode information, and allow for adaptive behaviors. We are developing and using small molecules to track the functional states of glutamate-gated ion channels at neuronal synapses.

Natural hormones, cellular metabolites, and other small molecules drive specific changes in the structure and activity of nuclear receptors. In response to ligand binding, nuclear receptors form protein complexes that control gene transcription events underlying development, homeostasis, and many diseases. We are designing small molecules to manipulate gene transcription by precisely controlling the activity of nuclear receptors.

Departmental research area

chemical biology and medicinal chemistry

My research expertise

Nuclear Receptors, Gene Transcription, androgen receptor, Antiandrogen, Nurr1, Nur77, Liver Receptor Homolog 1 (LRH1), dopamine, Glutamate, Ligand-gated Ion Channel, AMPA Receptor, Synaptic Transmission, Synaptic Plasticity, learning and memory, neurodegeneration, Parkinson’s disease

Professional background

Degrees

PhD, Chemistry, Massachusetts Institute of Technology (MIT), 1995
Bachelor of Science, Chemistry, University of California, Los Angeles, 1989

Biography

Research in the England Lab focuses on the development and use of small molecules to manipulate and monitor the activities of biologically important ligand-receptor systems. Execution of these research projects typically involves a combination of synthetic chemistry, computational chemistry, structural biology, and appropriate biochemical and biological assays. Two systems currently being studied are glutamate-gated ion channels and hormone-activated nuclear receptors.

The neurotransmitter glutamate drives specific changes in the functioning of synaptic glutamate-gated ion channels. These changes modulate the strength of synaptic transmission, encode information, and allow for adaptive behaviors. We are developing and using small molecules to track the functional states of glutamate-gated ion channels at neuronal synapses.

Natural hormones and other small lipophilic molecules drive specific changes in the structure and activity of nuclear receptors. In response to hormone binding, nuclear receptors form protein complexes that control gene transcription events underlying development, homeostasis, and many diseases. We are designing small molecules to manipulate gene transcription by precisely controlling the activity of nuclear receptors.

Research keywords

  • Androgen Antagonists
  • Indoles
  • Nitriles
  • Molecular Probes
  • Quinolines
  • dopamine
  • Anilides
  • Receptors, AMPA
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Enzyme Activators
  • Nitro Compounds
  • Disulfides
  • Tosyl Compounds
  • Excitatory Amino Acid Antagonists
  • Synapses
1. Update from the Dean – May 2019
2. 2019 Koda-Kimble Seed Award supports School of Pharmacy’s boldest ideas
3. School of Pharmacy scientists unearth a new target for treating Parkinson’s disease
4. Update from the Dean - Spring/Summer 2015
5. Innovation in Education Awards go to Shin, Jacobson, Ferrone
6. Update from the Dean - Spring/Summer 2007
7. Update from the Dean - Spring/Summer 2006
8. England receives McKnight Endowment Award
9. Memory-making molecules now better understood
10. Five pharmacy women at Mission Bay
11. About Leslie Wilson, and more news
12. Women of science make fall 2002 move to Mission Bay
13. Joanne Whitney and the DPSL, and more news
1. Dean's Award for Excellence in Teaching, UCSF, 2021
2. Dean’s Award for Excellence in Teaching, UCSF, 2021
3. CTSI Catalyst Award, UCSF, 2020
4. Dean’s Award for Excellence in Teaching, UCSF, 2019
5. Dean’s Award for Excellence in Teaching, UCSF, 2018
6. Roger's Family Foundation Bridging the GAP Award, UCSF, 2015
7. CTSI Catalyst Award, UCSF, 2014
8. McKnight Technological Innovations in Neuroscience Award, UCSF, 2006
9. Grass Foundation Fellowship, Caltech, 1998
10. NRSA Postdoctoral Fellowship, Caltech, 1997
11. Gosney Postdoctoral Fellowship, Caltech, 1996
12. Merck Index Award, UCLA, 1989
13. UCLA Chemists Association Award for Research, UCLA, 1989

Publications

Kholodar SA, Lang G, Cortopassi WA, Iizuka Y, Brah HS, Jacobson MP, England PM. Analogs of the Dopamine Metabolite 5,6-Dihydroxyindole Bind Directly to and Activate the Nuclear Receptor Nurr1. ACS Chem Biol. 2021 07 16; 16(7):1159-1163.
Bruning JM, Wang Y, Oltrabella F, Tian B, Kholodar SA, Liu H, Bhattacharya P, Guo S, Holton JM, Fletterick RJ, Jacobson MP, England PM. Covalent Modification and Regulation of the Nuclear Receptor Nurr1 by a Dopamine Metabolite. Cell Chem Biol. 2019 05 16; 26(5):674-685.e6.
de Jesus Cortez F, Nguyen P, Truillet C, Tian B, Kuchenbecker KM, Evans MJ, Webb P, Jacobson MP, Fletterick RJ, England PM. Development of 5N-Bicalutamide, a High-Affinity Reversible Covalent Antiandrogen. ACS Chem Biol. 2017 12 15; 12(12):2934-2939.
de Jesus Cortez F, Suzawa M, Irvy S, Bruning JM, Sablin E, Jacobson MP, Fletterick RJ, Ingraham HA, England PM. Disulfide-Trapping Identifies a New, Effective Chemical Probe for Activating the Nuclear Receptor Human LRH-1 (NR5A2). PLoS One. 2016; 11(7):e0159316.
England PM. Developing a photoreactive antagonist. Methods Mol Biol. 2013; 995:121-9.
Aungst S, England PM, Thompson SM. Critical role of trkB receptors in reactive axonal sprouting and hyperexcitability after axonal injury. J Neurophysiol. 2013 Feb; 109(3):813-24.
Harvey JH, Long DH, England PM, Whistler JL. Tuned-Affinity Bivalent Ligands for the Characterization of Opioid Receptor Heteromers. ACS Med Chem Lett. 2012 Aug 09; 3(8):640-644.
England PM. Bridging the gaps between synapses, circuits, and behavior. Chem Biol. 2010 Jun 25; 17(6):607-15.
Fleming JJ, England PM. AMPA receptors and synaptic plasticity: a chemist's perspective. Nat Chem Biol. 2010 Feb; 6(2):89-97.
Fleming JJ, England PM. Developing a complete pharmacology for AMPA receptors: a perspective on subtype-selective ligands. Bioorg Med Chem. 2010 Feb 15; 18(4):1381-7.
Wang X, Ratnam J, Zou B, England PM, Basbaum AI. TrkB signaling is required for both the induction and maintenance of tissue and nerve injury-induced persistent pain. J Neurosci. 2009 Apr 29; 29(17):5508-15.
Cruz LA, Estébanez-Perpiñá E, Pfaff S, Borngraeber S, Bao N, Blethrow J, Fletterick RJ, England PM. 6-Azido-7-nitro-1,4-dihydroquinoxaline-2,3-dione (ANQX) forms an irreversible bond to the active site of the GluR2 AMPA receptor. J Med Chem. 2008 Sep 25; 51(18):5856-60.
Argilli E, Sibley DR, Malenka RC, England PM, Bonci A. Mechanism and time course of cocaine-induced long-term potentiation in the ventral tegmental area. J Neurosci. 2008 Sep 10; 28(37):9092-100.
Kaneko M, Hanover JL, England PM, Stryker MP. TrkB kinase is required for recovery, but not loss, of cortical responses following monocular deprivation. Nat Neurosci. 2008 Apr; 11(4):497-504.
Nilsen A, England PM. A subtype-selective, use-dependent inhibitor of native AMPA receptors. J Am Chem Soc. 2007 Apr 25; 129(16):4902-3.
England PM. Rapid photoinactivation of native AMPA receptors on live cells using ANQX. Sci STKE. 2006 Apr 18; 2006(331):pl1.
Adesnik H, Nicoll RA, England PM. Photoinactivation of native AMPA receptors reveals their real-time trafficking. Neuron. 2005 Dec 22; 48(6):977-85.
Chen X, Ye H, Kuruvilla R, Ramanan N, Scangos KW, Zhang C, Johnson NM, England PM, Shokat KM, Ginty DD. A chemical-genetic approach to studying neurotrophin signaling. Neuron. 2005 Apr 07; 46(1):13-21.
Chambers JJ, Gouda H, Young DM, Kuntz ID, England PM. Photochemically knocking out glutamate receptors in vivo. J Am Chem Soc. 2004 Nov 03; 126(43):13886-7.
England PM. Unnatural amino acid mutagenesis: a precise tool for probing protein structure and function. Biochemistry. 2004 Sep 21; 43(37):11623-9.