CURRICULUM VITAE NAME - Department of Anatomy and Cell

CURRICULUM VITAE
NAME:
Feng-Chun Yang, M.D., PhD
ADDRESS:
Indiana University School of Medicine
Herman B Wells Center for Pediatric Research
Cancer Research Institute
1044 W. Walnut, Bldg. R-4, Room 427
Indianapolis, IN 46202
Phone: (317) 274-4178
Fax: (317) 274-8928
Email: [email protected]
EDUCATION:
1983
M.D., Hebei Medical University
1996
Ph.D. – Hematology/Oncology, Shinshu University
ACADEMIC APPOINTMENTS:
1983 - 1991
Resident, Pediatric Fellow & Instructor, Central Hospital, Shijiazhuang, China
1996 - 1998
Research Fellow, Japanese Society for the Promotion of Science, The Institute
of Medical Science, University of Tokyo, Japan (with Dr. T. Nakahata)
1998 - 2001
Postdoctoral Research Fellow, Howard Hughes Medical Institute
2001 - 2004
Research Associate Herman B Wells Center for Pediatric Research, Indiana
University School of Medicine, Indianapolis, Indiana
2004 - 2005
Assistant Research Professor, Herman B. Wells Center for Pediatric
Research, Indiana University School of Medicine, Indianapolis, Indiana
2005 – Present Assistant Professor, Herman B Wells Center for Pediatric Research, Indiana
University School of Medicine, Indianapolis, Indiana
2007 – Present Adjunct Assistant Professor, Department of Anatomy and Cell Biology, Indiana
University School of Medicine, Indianapolis, Indiana
2006 – Present Honorary Professorship, Hebei Medical University, China
PROFESSIONAL ORGANIZATIONS:
1998 - Present American Society of Hematology
1998 - Present International Society for Experimental Hematology
2009 -Present American Society for Bone and Mineral Research
Selected Peer Reviewed Publications (since 2006):
1. F-C Yang, S. Chen, T. Clegg, X. Li, T. Morgan, S.A. Estwick, J. Yuan, W. Khalaf, S. Burgin,
J. Travers, L.F. Parada, D.A. Ingram, and D.W. Clapp. Nf1+/- mast cells induce
Feng-Chun Yang, CV, 1
neurofibroma like phenotypes through secreted TGF-b signaling. Human Molecular
Genetics 16:1-17 2006
2. F-C Yang, S. Chen, A.G. Robling, X. Yu, T.D. Nebesio, J. Yan, T. Morgan, X. Li, Jin Yuan,
J. Hock, D.A. Ingram and D.W. Clapp. Hyperactivation of p21ras and PI3-K cooperate to
alter murine and human NF1 haploinsufficient osteoclast functions. Journal of Clinical
Investigation 116:2880-2891 2006
3. X. Wu, S.A. Estwick, S. Chen, W. Ming, T.D. Nebesio, Y. Li, J. Yuan, K. Reuben, D. Ingram,
M.C. Yoder, F-C Yang. Neurofibromin plays a critical role in modulating osteoblast
differentiation of mesenchymal stem /progenitor cells. Human Molecular Genetics 15:28372845, 2006.
4. A.M. Munchhof, F. Li, H.A. White, L.E. Mead, T.R. Krier, A. Fenoglio, X. Li, J. Yuan, F-C
Yang and D.A. Ingram. Neurofibroma-associated growth factors activate a distinct
signaling network to alter the function of neurofibromin-deficient endothelial cells. Human
Molecular Genetics 15:1858-1869, 2006
5. F. Li, A.M. Munchhof, H.A. White, L.E. Mead, T.R. Krier, A. Fenoglio, S. Chen, X. Wu, S.
Cai, F-C Yang and D.A. Ingram. Neurofibromin is a novel regulator of RAS-induced signals
in primary vascular smooth muscle cells. Human Molecular Genetics 15:1921-1930, 2006
6. L.S. Haneline, H. White, F-C Yang, S. Chen, C. Orschell, R. Kapur, and D.A. Ingram.
Genetic reduction of class IA PI-3 kinase activity alters fetal hematopoiesis and competitive
repopulating ability of hematopoietic stem cells in vivo. Blood 107:1375-1382, 2006
7. Si Y, Ciccone S, F-C Yang, Yuan J, Zeng D, Chen S, van de Vrugt H, Critser J, Arwert F,
Haneline LS, Clapp DW. Related Articles, Links Continuous in vivo infusion of interferongamma (IFN-{gamma}) enhances engraftment of syngeneic wild-type cells in Fanca-/- and
Fancg-/- mice. Blood. 108:4283-4287, 2006
8. Nebesio TD, Ming W, Chen S, Clegg T, Yuan J, Yang Y, Estwick SA, Li Y, Li X, Hingtgen
CM, F-C Yang. Neurofibromin-deficient Schwann cells have increased lysophosphatidic
acid dependent survival and migration-implications for increased neurofibroma formation
during pregnancy. Glia. 55:527-536. 2007
9. Khalaf WF, F-C Yang, Chen S, White H, Bessler W, Ingram DA, Clapp DW. K-ras Is
Critical for Modulating Multiple c-kit-Mediated Cellular Functions in Wild-Type and Nf1+/Mast Cells. J Immunol. 178:2527-2734, 2007
10. B. Li, N. Jia, D.L. Waning, F-C Yang, L.S. Haneline, K.T. Chun. Cul4A is required for
hematopoietic stem cell engraftment and self-renewal. Blood 2007
11. J. Yan, S. Chen, Y. Zhang, Y. Li, X. Li, J. Yuan, S. Estwick, A. Robling, R. Kapur, R.J.
Chan, F-C Yang. Rac1, but not Rac2, mediates osteoclast gain-of-function induced by Nf1
haploinsufficiency. Hum Mol Genet, 2008
12. Goodman ML, Chen S, F-C Yang, Chan RJ. Novel Method of Murine Embryonic Stem CellDerived Osteoclast Development. Stem Cells Dev. 2008
13. Perry BC, Zhou D, Wu X, Yang F-C, Byers MA, Chu TM, Hockema JJ, Woods EJ, Goebel
WS. Collection, cryopreservation, and characterization of human dental pulp-derived
mesenchymal stem cells for banking and clinical use. Tissue Eng Part C Methods. 2008
Jun;14(2):149-56
14. Pulliam AC, Hobson MJ, Ciccone SL, Li Y, Chen S, Srour EF, Yang FC, Broxmeyer HE,
Clapp DW. AMD3100 synergizes with G-CSF to mobilize repopulating stem cells in Fanconi
anemia knockout mice. Exp Hematol. 2008 Sep;36(9):1084-90
15. F-C Yang, D.A. Ingram, S. Chen, Y. Zhu, J. Yuan, X. Li, X. Yang, S. Knowles, W. Horn, Y.
Li, S. Zhang, S.T. Vakili, M. Yu, D. Burns, K. Robertson, G. Hutchins, L.F. Parada, D.W.
Feng-Chun Yang, CV, 2
Clapp. NF1 tumor suppressor haploinsufficient bone marrow complements nullizygous
Schwann cells to form plexiform neurofibromas. CELL 135:437-448, 2008
16. Munugalavadla V, Vemula S, Krishnan S, Sims EC, Chen S, Yan J, Li H, Niziolek PJ,
Takemoto C, Robling AG, Yang FC, Kapur R. p85{alpha} subunit of class IA PI-3Kinase
regulates the expression of multiple genes involved in osteoclast maturation and migration.
Cell Biol. 28:7182-7198, 2008
17. Li Y, Chen S, Yuan J, Yang Y, Li J, Ma J, Wu X, Freund M, Pollok K, Hanenberg H, Goebel
WS, Yang FC. Mesenchymal stem/progenitor cells promote the reconstitution of
exogenous hematopoietic stem cells in Fancg-/- mice in vivo. Blood 2009 Mar
5;113(10):2342-51. Epub 2009 Jan 7
18. H. Li, Y. Liu, Q. Zhang, Y. Jing1, S. Chen, Z. Song, J. Yan, Y. Li, X. Wu, X. Zhang, Y.
Zhang, J. Case, M. Yu, DA. Ingram, F-C Yang. Ras dependent paracrine secretion of
osteopontin by Nf1+/- osteoblasts promote osteoclast activation in a neurofibromatosis type
I murine model. Pediatric Res. 2009 Jun;65(6):613-8.
19. Elefteriou F, Kolanczyk M, Schindeler A, Viskochil DH, Hock JM, Schorry EK, Crawford AH,
Friedman JM, Little D, Peltonen J, Carey JC, Feldman D, Yu X, Armstrong L, Birch P,
Kendler DL, Mundlos S, Yang F-C, Agiostratidou G, Hunter-Schaedle K, Stevenson
DA.Skeletal abnormalities in neurofibromatosis type 1: approaches to therapeutic options.
Am J Med Genet A. 2009 149A(10):2327-38
20. Benson EA, Goebl MG, Yang F-C, Kapur R, McClintick J, Sanghani S, Clapp D and
Harrington M. Loss of SIMPL Compromises TNFα Dependent Survival of Hematopoietic
Progenitors. Exp Hemato 2009 (in press)
21. H. Hirasawa, C. Jiang, P. Zhang, Yang F-C, H. Yokota. Mechanical stimulation suppresses
phosphorylation of eIF2a and PERK-mediated responses to stress to the endoplasmic
reticulum. FEBS Letters 2010, 584: 745–752
22. Staser K, Yang FC, Clapp DW. Mast cells and the neurofibroma microenvironment. Blood.
2010 March 16.
23. Nebesio T., Chen S., Yang FC. What accounts for the variable responses to progesterone
on Schwann cells from mice and humans – the species-specific influence or the paracrine
effects from the tumor microenvironment? Cancer Biology & Therapy 10:11, 1-2 2010
24. Chen S., Burgin S., McDaniel A, Li X., Yuan J, Chen M, Khalaf W, Clapp DW, and Yang FC.
Nf1-/- Schwann cell conditioned medium modulates mast cell degranulation by C-Kit
mediated hyperactivation of PI-3 kinase. American Journal of Pathology 2010 (accepted).
Grant source
ACTIVE
NF073112
02/01/08-02/28/11
Department of Defense (PI-Yang)
$174,993/year
Identification of the cellular and molecular mechanisms underlying the osseous manifestations
of NF1 in murine and human systems
Goals: To generate a murine model that recapitulates the scoliosis and osteoporosis
manifestations prevalent in NF1 patients, and to identify the role of Ras/Erk signaling axis on
murine and human OBL progenitors development.
Feng-Chun Yang, CV, 3
06/01/08-05/31/11
March of Dimes Birth Defects Foundation (PI-Yang) $78,373/year
Genetic, Functional, and Biochemical Characterization of Neurofibromin Dependent Skeletal
Dysplasias Utilizing Murine Models
The goal of this application is to test the hypothesis that nullizygous loss of Nf1 in
preosteoblasts/osteoblasts and haploinsufficiency of Nf1 in other lineages (Nf1+/-;ob-/-) are
collectively necessary and sufficient to induce pathological changes in skeletal biomechanics
and signaling pathways mediating the pathogenesis.
R01 CA074177-13 (PI-Clapp, Yang-co-PI)
05/01/08-02/28/13
NIH
$223,789/year
Neurofibromatosis Type 1 Gene Regulates Myelopoiesis
This grant examines the effect of genetic inactivation of RAC proteins on neurofibromin
deficient myeloid cells.
Role: Co-Investigator
08/01/08-07/31/11
Doris Duke Research Foundation (PI-Stevenson, Co-PI-Yang)
$22,784/year
Effects of Germline Mutations within the Ras Pathway on Bone Remodeling
The goal of this study is to determine how PTPN11 and NF1 mutations affect osteoclast
function and bone abnormalities in individuals with Noonan syndrome and Neurofibromatosis
type 1, respectively.
Role: Co-Investigator
U01 NS055849-02 (PI-Clapp, Yang, co-PI)
07/01/08-06/30/12
NIH-NINDS
$415,563/year
Preclinical Testing of Targeted Therapies for Neurofibromas
Goals: Evaluation of experimental compounds in a preclinical model of plexiform neurofibromas
Role: Co-Investigator, Group Leader for Team 2
W81XWH-09-1-0120 (PI-Robertson, Yang Co-I)
04/01/09-03/31/12
DOD
$250,000/year
Pilot Study Of Gleevec®/Imatinib Mesylate (STI-571, NSC 716051) In Neurofibromatosis (NF1)
Patients With Plexiform Neurofibromas
The major goal of this project is to test the use of known therapeutic agents on a novel use i.e.,
shrinkage of tumors in patients with neurofibromatosis. We will also pilot a NF-specific health
related quality of life tool.
Role: Co-Investigator
P50 NS 052606-04 (PI-Parada, Yang-Multi-PI project 2)
07/01/10 – 06/30/15
NIH/NINDS/UTSW
$211,525/year
Role of hematopoietic microenvironment in plexiform neurofibroma progression
Goals: Evaluate the role of monocyte/ macrophages in plexiform neurofibroma formation
R01 (Yang-Multi-PI with Drs. Clapp & Hanenberg) 12/01/2010-11/30/2015
NIH
$250,000/year
Genetic Therapy for Fanconi Anemia
Feng-Chun Yang, CV, 4
PENDING:
W81XWH-10-NFRP-IIFRA (Yang)
09/30/11-09/29/14
DOD
$223,204
Identifying molecular and pharmacologic targets for impaired healing in a murine model of NF1
Goals: The studies proposed here will allow us to further test potential therapeutics for the
treatment of non-union fracture healing using both genetic murine models and pharmacologic
inhibitors. By completing our studies, we will be able to answer whether genetic or
pharmacologic targeting of our hypothesized pathway improves fracture healing in a murine
model of NF1.
DOD (PI-Yang)
12/01/10-11/30/13
$250,000/annual
Title: Identifying molecular and pharmacologic targets for impaired fracture healing in murine
model of NF1.
RO1 (PI-Yang)
07/01/11-06/30/16
$250,000/annual
Title: Neurofibromin controls fracture healing
Previous Support:
Investigating the functional role of microenvironment in supporting hematopoiesis utilizing
Fancg-/- murine model. Simmons grant. $25,000 PI - FC Yang
Evaluation of the Role of Haploinsufficiency of NF1 in Modulating Osteoclast Cell Fates and
Skeletal Formation. Research Support Funds Grant (RSFG) $30,000 PI – FC Yang
Identification of the biochemical mechanisms underlying the pathological increase in de novo
cytokine production in murine Nf1+/- mast cells and human NF1 mast cells. Department of
Defense (W81XWH-05-1-0161, NF043032), Annual Direct Costs $150,000.00/yr. PI – FC Yang
From Animal Models To Therapeutics, University of Texas Southwestern, P50 NS052606,
Project 3, 7/1/05 – 6/30/10, Annual Direct Costs, $378,750. PI DW Clapp. Co-PI – FC Yang
Feng-Chun Yang, CV, 5