Steven H. Liang, PhD

Steven H. Liang, PhD

Assistant Professor of Radiology, HMS
Assistant Chemist, MGH

Email:   liang.steven@mgh.harvard.edu
Phone:   1-617-726-3404


Biography

I obtained my B.Sc (Honors) in chemistry at Tianjin University in 2003, followed by one year industry practice on the peptide synthesis. In 2004, I moved to Canada and pursued my Ph.D under the supervision of Professor Marco Ciufolini, Canada Research Chair in Synthetic Organic Chemistry, at the University of British Columbia. My doctoral research mainly focuses on natural product and analog synthesis for pharmaceutical application. It has involved (1) the synthesis of analogs of the antifungal natural product sordarin, in collaboration with Bayer CropScience; (2) development and optimization of intramolecular and bimolecular oxidative amidation, and application of this methodology to the total synthesis of (+)-lepadiformine, a potassium channel blocker, and to synthetic studies of tetrodotoxin and himandrine; (3) the synthesis of three fragments of the anticancer natural product diazonamide B. I have also devoted myself to independent research that has resulted in several articles as the corresponding author, for instance, (1) topic on synthesis of fully functionalized oxazoles in Current Organic Chemistry; (2) topic on antifungal natural product sordarin in Beilstein Journal of Organic Chemistry (one of the five most accessed articles in October 2008, 4400+ times open-accessed as of Nov 2011) and two chemical reagent reviews in Synlett. In early 2010, I started a new journey in the laboratory of Professor Elias J. Corey, Noble Laureate in Chemistry, in the Department of Chemistry and Chemical Biology at Harvard University. My postdoctoral research centers on the innovation of silicon-based reagents and their applications in natural product and bioactive analog synthesis. One of my contributions is the invention and commercialization of a new silyl protective reagent, which is highlighted on C&EN News, Synform and top one of most-read articles on Organic Letters in 2011.

In mid 2012, I accepted a junior faculty position in the Department of Radiology, Harvard Medical School and in the Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital. My organic synthesis experience and skills enable me to develop novel radiochemistry methods, labeled compounds and radiopharmaceuticals with 11C and 18F aimed at clinical applications in human subjects. Our recent projects are focused on: (1) a novel method of labeling the mGluR5 antagonist [18F]FPEB for in vivo quantitation of such receptor levels in patients suffering from Alzheimer’s Disease (AD) and (2) a new concept of  “Flow Hydrogenation in Radiochemistry” and its application of the automated radiosynthesis of [18F]CABS13 – the first PET radiotracer to explore the metals hypothesis of Alzheimer's disease; (3) new [11C]CO2 fixation and 11C-methylation reactions to prepare neuroimaging agents; (4) new methods for radiolabeling non-activated aromatics including [18F]fluoro-L-Dopa and (5) directly labeling pharmaceutical compounds with 11C or 18F without changing the chemical structure for pharmacokinetic studies.

Education

  • B.Sc. in Chemistry, 2003, Tianjin University, Tianjin, P.R. China
  • Ph.D in Chemistry, 2010, University of British Columbia, Vancouver, B.C., Canada - Advisor: Professor Marco Ciufolini

Professional Positions

  • NSERC Postdoctoral Fellow, 2010 – 2012, Department of Chemistry and Chemical Biology, Harvard University, MA - Advisor: Professor E.J. Corey
  • Associate, 2012 – Present, Department of Chemistry and Chemical Biology, Harvard University, MA
  • Assistant in Chemistry, 2012 – Present, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, MA
  • Instructor in Radiology, 2012 – 2013, Department of Radiology, Harvard Medical School, Boston, MA
  • Assistant Professor of Radiology, 2013 – Present, Department of Radiology, Harvard Medical School, Boston, MA

Awards

  • 2014 First Place, Young Investigator Award, Society of Nuclear Medicine (Radiopharmaceutical Sciences Council)
  • 2014 The Dr. Michael J. Welch Foundation Travel Grant
  • 2013 Alzheimer’s Drug Discovery Foundation Young Investigator Award
  • 2013 Drew University Resident School of Medicinal Chemistry Scholarship
  • 2012 American Chemical Society, Center for Professional Development Scholarship
  • 2010 Postdoctoral Fellowship by Natural Sciences and Engineering Research Council of Canada
  • 2009 American Chemical Society, Division of Organic Chemistry Travel Award
  • 2009 University of British Columbia Graduate Travel Award
  • 2008 Chinese Government Excellent Overseas Student Award
  • 2008 Gladys Estella Laird Research Fellowship
  • 2008 University of British Columbia Graduate Fellowship
  • 2007 University of British Columbia Department of Chemistry Travel Fund
  • 2004 University of British Columbia Ph.D. Tuition Award
  • 2003 Excellent Student Award, Tianjin University
  • 2002 Takeda Scholarship
  • 2001 K.C. Wong Memorial Scholarship

 

Publications since joining MGH

  • B. Rotstein, N. Stephenson, N. Vasdev* and S.H. Liang* “Spirocyclic hypervalent iodine(III)-mediated radiofluorination of non-activated and hindered aromatics” Nature Communications 2014, 5, 4365-4369. DOI:10.1038/ncomms5365
    Abstract: We describe an effective solution that relies on the chemistry of spirocyclic hypervalent iodine(III) complexes, which serve as precursors for rapid, one-step regioselective radiofluorination with [18F]fluoride.
  • S.H. Liang* and N. Vasdev* “Aliphatic 18F Bond Formation via Transition Metal Based [18F]Fluorination” Angewandte Chemie International Edition 2014, in press
    Abstract: Recent advances in aliphatic radiofluorinations enabled by transition metals, specifically Co- and Mn-salen complexes, have been unveiled. These new approaches operate in a unique way that obviates the need of highly activated substrates for radiolabeling and offers a new synthetic strategy to prepare 18F-labeled radiotracers.
  • T. Kasahara, Y.J. Jang, L. Racicot, D. Panagopoulos, S.H. Liang and M.A. Ciufolini* “Iodonium Metathesis Reacions” Angewandte Chemie International Edition 2014, in press. DOI: 10.1002/anie.201405594
    Abstract: A metathesis reaction occurs when a diaryliodonium triflate is heated with an aryl iodide, resulting in the formation of a new diaryliodonium triflate.
  • B. Rotstein, H. Wey, T. Shoup, A. Wilson, S.H. Liang, J. Hooker* and N. Vasdev* “PET Imaging of Fatty Acid Amide Hydrolase with [18F]DOPP in Non-Human Primates” Molecular Pharmaceutics 2014, in press. DOI: 10.1021/mp500316h
    Abstract: The goal of this work is to evaluate [18F]DOPP in  nonhuman primates to support its clinical translation for the imaging of fatty acid amide hydrolase (FAAH).
  • S.H. Liang, D.L. Yokell, M.D. Normandin, P.A. Rice, R.N. Jackson, T.M. Shoup, T.J. Brady, G. El Fakhri,      T.L. Collier* and N. Vasdev* “First Human Use of a Radiopharmaceutical Prepared by Continuous-Flow Microfluidic Chemistry: Proof of Concept with the Tau Imaging Agent [18F]T807”. Molecular Imaging 2014, in press
    Abstract
    : The goal of this study was to validate the synthesis of the tau radiopharmaceutical 7-(6-fluoropyridin-3-yl)-5H-pyrido[4,3-b]indole ([18F]T807) and perform a first in human PET scan enabled by microfluidic flow chemistry.
  • B. Rotstein, S.H. Liang and N. Vasdev* “Clinical PET Research Realized by [11C]CO2-Fixation” Molecular Imaging Gateway Newsletter, 2014, 8, issue 2. [link]
    Abstract: In this article, we present a summary of modern [11C]carbon dioxide-fixation reactions that have enabled new classes of radiotracers to be explored in preclinical and clinical research studies.
  • J.P. Holland, S.H. Liang, B. Rotstein, T.L. Collier, N. Stephenson, I. Greguric and N. Vasdev* “Alternative approaches for PET radiotracer development in Alzheimer’s disease: Imaging beyond plaque” Journal of Labelled Compounds and Radiopharmaceuticals 2014, 57, 323-331. DOI: 10.1002/jlcr.3158
    Abstract: We present the chemical basis of various radiotracers which show promise in preclinical or clinical studies for use in evaluating the phenotypic or biochemical characteristics of AD. Radiotracers for PET imaging neuroinflammation, metal ion association with Aβ-plaques, tau protein, cholinergic and cannabinoid receptors, and enzymes including glycogen-synthase kinase-3β and monoamine oxidase B amongst others, and their connection to AD are highlighted.
  • B. Rotstein, J. Hooker, J. Woo, T. Collier, T. Brady, S.H. Liang* and N. Vasdev* “Synthesis of [11C]bexarotene by Cu-mediated [11C]carbon dioxide fixation and preliminary PET imaging” ACS Medicinal Chemistry Letters 2014, 5, 668-672. DOI: 10.1021/ml500065q
    Abstract: We use 11CO2 fixation technology to produce 11C-labeld bexarotene (Targretin™), a retinoid X receptor agonist that has proposed mechanisms of action in Alzheimer’ s disease that have been the subject of recent controversy.
  • The research was highlighted on ACS Medicinal Chemistry Letters as a journal cover and featured by The Cutting Edge of Chemistry – A Pharma Matters Report, Thomson Reuters, June 2014.
  • S.H. Liang, D. Yokell, R. Jackson, P. Rice, R. Callahan, K. Johnson, D. Alagille, G. Tamagnan, T. Collier* and N. Vasdev* “Microfluidic continuous-flow radiosynthesis of [18F]FPEB suitable for human PET imaging” Medicinal Chemistry Communications 2014, 5, 432-435. DOI: 10.1039/C3MD00335C
    Abstract: The synthesis of fluorine-18 labeled 3-fluoro-5-[(pyridin-3-yl)ethynyl] benzonitrile ([18F]FPEB) for imaging metabotropic glutamate receptor subtype type 5 (mGluR5) was achieved with a commercial continuous-flow microfluidics device, which represents the first positron emission tomography (PET) radiopharmaceutical that is suitable for human use with this technology.
  • S.H. Liang, T. Collier, B. Rotstein, R. Lewis, M. Steck and N. Vasdev* “Rapid Microfluidic Flow Hydrogenation for Reduction or Deprotection of 18F-Labeled Compounds.” Chemical Communications 2013, 49, 8755-8757. DOI: 10.1039/C3CC45166F
    Abstract: The goal of the present work was to enable transition-metal based microfluidic flow hydrogenation as a viable tool for reduction and deprotection reactions in the synthesis of PET radiotracers.
  • B. Rotstein, S.H. Liang, J. Holland, T. Collier, J. Hooker, A. Wilson and N. Vasdev* “11CO2 Fixation: A Renaissance in PET Radiochemistry.” Chemical Communications 2013, 49, 5621-5629. DOI: 10.1039/C3CC42236D
    Abstract: This review summarizes classical [11C]CO2 fixation strategies using organometallic reagents and then focuses on newly developed methods that employ strong organic bases to reversibly capture [11C]CO2 into solution, thereby enabling highly functionalized labelled compounds to be prepared.