Yichin Liu, Ph.D.
Current Contact Information:
Yichin Liu, Ph.D.
Tel. 805-313-5316
E-mail:
yichinl@amgen.com
EDUCATION
Yale University New Haven, CT
Ph.D. in Chemistry (2000)
Massachusetts Institute of Technology Cambridge, MA
Bachelor of Science in Chemistry (June 1995)
Minor in Literature (June 1995)
Concentration in Women's Study (June 1995)
POSTDOCTORAL TRAINING
Brigham & Women’s Hospital/Harvard Medical School Cambridge, MA
Research Fellow in Neurology (September 2000 – present)
AWARDS AND HONORS
NIH Postdoctoral Fellowship (December 2001 – present)
Harvard Neurodegeneration Training Grant Postdoctoral Fellowship (2001)
Pfizer Predoctoral Fellowship (1995 – 2000)
Merck Index Award (1995)
CURRENT RESEARCH
Discovery of a novel enzymatic activity of UCH-L1.
A mutation (I93M) of the neuronal ubiquitin C-terminal hydrolase (UCH-L1) has been linked to a rare early-onset form of Parkinson’s disease (PD), at the same time a polymorphism of the enzyme (S18Y) was indicated to reduce the risk of PD. UCH-L1 hydrolyzes C-terminal ester and amides of ubiquitin and is believed to play a key role in processing polyubiquitin and/or ubiquitylated proteolytic peptide. Recently, we have demonstrated that UCH-L1 can form dimer which is capable of ubiquitin ligation activity. We believe that this activity may play a significant role in PD pathogenesis. (see Liu, et al, Cell 2002).
HTS discovery of UCH-L1 hydrolase inhibitors and activators.
We have undertaken a multi-pronged high-throughput screening (HTS) approach designed to identify drug-like molecules ("molecular probes") that can be used to perturb UCH-L1 enzymatic activity both in vitro and in cell culture and animal models of PD (Submitted to Chemistry & Biology).
Probing the natural functions of UCH-L1 in neurons and cancer cells.
Using RNAi technique and the UCH-L1 inhibitors discovered from HTS, UCH-L1’s natural functions in neuronal cell (SH-SY5Y) line and UCH-L1 positive lung cancer cell lines are being investigated.
GRADUATE RESEARCH
Primary Investigator: Professor Alanna Schepartz, Yale University
Doctoral Thesis: Yichin Liu. “Kinetic and Thermodynamic Studies on DNA Recognition by Transcription Factors and Miniature Peptides.” Department of Chemistry, Yale University, New Haven, CT. 2000
1. Studied the kinetics and equilibria of bidirectional bindings of the TATA box binding protein (TBP) to the TATA box DNA using Fluorescence Resonance Energy Transfer (FRET).
2. Studied DNA-binding of designed peptides to a specific DNA target site using isothermal titration calorimetry.
3. Probed the basic region-leucine zipper (bZIP) peptide-Hepatitis B virus X protein interaction using combinatorial peptide chemistry.
4. Studied the mechanism of DNA bending by bZIP family of eukaryotic transcription factors.
UNDERGRADUATE RESEARCH
Professor Robert Langer's Laboratory, MIT (1993 – 1994)
Research assistant in aiding the synthesis and cell toxicity analysis of an RGD modified lactic acid-co-lysine polymer for use as a bioresorbable scaffold designed for cell transplantation.
Professor William H. Orme-Johnson's Laboratory, MIT (1992 – 1993)
Research assistant in the study of the three-dimensional structure of the enzyme lanosterol-14-a-demethylase.
PUBLICATIONS
Liu Y, Lashuel HA, Choi S, Xing X, Case A, Ni J, Yeh L-A, Cuny GD, Stein RL, and Lansbury Jr. PT, A class of small molecule UCH-L1 inhibitors: Chemical genetic tools to probe pathogenesis of Parkinson’s disease and cancer. Submitted to Chemistry & Biology.
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Work featured in the News |
"Biotech Thinking Comes to Academic Medical Centers" (Science) By Joe Alper, Science 2003 Feb 28 (299)1303-5
http://www.sciencemag.org/cgi/content/full/299/5611/1303?ijkey=jKcQnDrJypXr6&keytype=ref&siteid=sci
Liu Y, Fallon L, Lashuel HA, Liu Z, and Lansbury Jr. PT, The UCH-L1 gene encodes two opposing enzymatic activities that affect a-synuclein degradation and parkinson's disease susceptibility. Cell 2002 (111) 209-218.
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Work featured in the News |
"Gene Study Reveals Clues to Parkinson's Disease" (Health – Reuters) By Keith Mulvihill, October 18, 2002.
http://story.news.yahoo.com/news?tmpl=story&u=/nm/20021018/hl_nm/parkinsons_gene_dc_1
"Jeckyl and Hyde: Protein Degradation in Parkinson's Just Added New Player, Or Did It?" (Alzheimer’s Research Forum) By Gabrielle Strobel, October 21, 2002.
http://www.alzforum.org/new/detail.asp?id=685
"Deadly Giveaway, Protein linked to Parkinson's disease squanders clearance molecules."(Science) By John R. Davenport. Science Magazine October 23, 2002.
http://sageke.sciencemag.org/cgi/content/abstract/sageke;2002/42/nw145.
"Enzyme Linked to Pathology of Parkinson's Disease Appears Two-faced."(Focus) By Courtney Humphries, November 8, 2002.
http://focus.hms.harvard.edu/2002/Nov8_2002/neurology.html
Liu M, Liu Y, Doulatov SR, Baker S, Davis P, Simmonds M, Preston A, Maskell D, Harvill ET, Parkhill J, Miller JF. Complete nucleotide sequence, molecular analysis and genome structure of related Bordetella bacteriophage BPP-1, BIP-1, and BMP-1. Manuscript in preparation.
Liu Y, Schepartz A. Kinetic preference for oriented DNA binding by the yeast TATA-binding protein TBP, Biochemistry 2001 (40) 6257-6266.
Paolella DN, Liu Y, Fabian MA, Schepartz A. Electrostatic mechanism for DNA bending by bZIP proteins. Biochemistry 1997 (36) 10033-10038.
PRESENTATIONS
"UCH-L1 and Parkinson’s disease", Oral and poster presentations in The 4th Annual Meeting of the Udall Centers of Excellence for Parkinson’s Disease Research, Boston Massachusetts, USA, August 11-13, 2002
"Atypical ubiquityl ligase activity of UCH-L1 may explain its link to Parkinson's disease susceptibility", Poster presentation in The 8th International Conference on Alzheimer's Disease and Related Disorders, Stockholm Sweden, July 21-25, 2002
"A novel role for UCH-L1 in Parkinson's disease", Oral presentation in Movement Disorders Conference at Massachusetts General Hospital, Boston Massachusetts, USA, October 4, 2001
"Neuronal ubiquitin c-terminal hydrolase (UCH-L1) has previously unrecognized ubiquitin ligase activity that is decreased by a Parkinson's disease-associated mutation", Poster presentation in The First Annual Udall Parkinson's Disease Centers of Excellence Poster Session, Boston Massachusetts, USA, June 7, 2001
TEACHING EXPERIENCES
1. Yale University Department of Chemistry (Sept 1995 - Dec 1996)Teaching Assistant in Organic Chemistry
2. MIT Department of Chemistry (Sept 1994 - Dec 1994) Teaching Assistant in Organic Chemistry
3. MIT Tutorial Service (Sept 1993 - Dec 1993) Math and Chemistry Tutor
4. MIT Department of Civil Engineering (Jan 1993 - May 1993) Grader for Computer Science Course
5. MIT Experimental Study Group (Sept 1992 - Jan 1993) Math Tutor in Calculus and Differential Equations
