BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Puri, Neelu
Associate Professor
eRA COMMONS USER NAME (credential, e.g., agency login)
N-PURI
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and
residency training if applicable.)
DEGREE
INSTITUTION AND LOCATION
MM/YY
FIELD OF STUDY
(if applicable)
University of Delhi, Delhi, India
M.Sc.
1979
University of Delhi, Delhi, India
M.Phil.
1980
All India Institute of Medical Sciences, New Delhi,
India.
Ph.D.
1989
Molecular Biology and
Biochemistry
Molecular Biology and
Biochemistry
Biochemistry
A. Personal Statement
My research focuses on two major areas:
1) Cancer therapy:
T-oligo: My cancer therapy research focuses on developing novel targeted therapies using T-oligo. We have
found T-oligo (nucleotides homologous to the telomere overhang) to be therapeutically effective in lung cancer
and melanoma cells and pre-established tumor xenografts by inducing apoptosis and senescence. We are
currently attempting to deliver T-oligo as a nanoparticle complexed with a cationic peptide to melanoma tumors
in mice.
Lung Cancer: My project on lung cancer aims to unravel the mechanism of EGFR/c-Met tyrosine kinase
inhibitor (TKI) resistance in Non-Small Cell lung cancer by studying the signaling pathways in resistant and
parental NSCLC cell lines with and without EGFR TK mutations. Recent studies in our lab demonstrate
activation of alternative signaling pathways in resistant cell lines which can be targeted along with EGFR and
c-Met pathways to overcome or delay the TKI resistance. Currently, we are also investigating the role of
epithelial mesenchymal transition in the development of resistance in NSCLC. Our translational research
focuses on identifying the role of biomarkers EGFR/c-Met and key proteins from the mTOR and Wnt signaling
pathways, in prognosis of NSCLC patients using immunohistochemistry.
Melanoma: My cancer research also focuses on melanoma, where we have successfully evaluated the role of
c-Met as a molecular target in melanoma. We are currently investigating the mechanism and TKI combination
therapies to overcome c-Met and BRAF resistance in wild type and melanoma cell lines with a BRAF mutation.
2) Role of FTO in obesity:
This project aims at identifying the role of FTO in promoting obesity in humans. We have downregulated FTO
with siRNA and using a microarray studied affected genes. We have constructed a pathway from the
microarray data and are currently identifying key targets. We are investigating the mechanism of how FTO
induces obesity. Our recent studies indicate that FTO modulates intracellular energy levels and downstream
signaling mechanisms which control energy intake and metabolism.
B. Positions and Honors
Positions and Employment
1990-1994
Scientist, Dept. of Dermatology, Academic Medical, Univ. of Amsterdam, Amsterdam, The
Netherlands.
1994-1996
Post Doc, The Wistar Institute of Anatomy and Biology, Affiliated with Univ of Pennsylvania, PA.
1996-1997
Research Associate, Fox Chase Cancer Center, Philadelphia, PA
1997-1998
Assistant Researcher, University of Arizona Health Sciences Center, Tucson, AZ.
1998-2003
Research Associate, Boston University Medical Centre, Boston, MA
2003-2007
Research Associate, University of Chicago, Chicago, IL
2008-2014
Assistant Professor University of Illinois, Rockford College of Medicine, Rockford, IL
2014-Present Associate Professor University of Illinois, Rockford College of Medicine, Rockford, IL
Honors
National Independent Fellowships Obtained:
1.
Research Associate from CSIR. (Council of Scientific & Industrial Research, India)
2.
Research Associate from ICMR. (Indian Council of Medical Research, India)
3.
Senior Research Fellowship from ICMR and Junior Research Fellowship from CSIR.
Awards/Prizes/Projects Received:
1.
Travel award from Pan American Society for Pigment Cell Research to attend XVth IPC Conference in
London.
2.
Travel awards from International Pigment Cell Society and Council of Scientific and Industrial, New
Delhi to attend XIVth IPC Conference in Kobe, Japan.
3.
Travel award from International Pigment Cell Society to attend the XVIth IPC Conference in Anaheim,
USA.
4.
Independent Research Project from the Department of Science and Technology, Government of India
on 'Immunological Basis of Vitiligo'.
5.
University of Delhi science merit award.
6.
Presented a plenary lecture at the symposium on cutaneous and ocular melanoma; genetics and basic
biology at the 18th international pigment cell conference, 2002, Amsterdam, The Netherlands.
7.
Best Poster Award on 13th annual research day March 2008, at University of Illinois.
8.
Faculty Support Scholarship Award, University of Illinois College of Medicine at Rockford, Rockford, IL,
USA, 2009.
9.
Faculty Support Scholarship Award, University of Illinois College of Medicine at Rockford, Rockford, IL,
USA, 2012.
10.
Faculty Support Scholarship Award, University of Illinois College of Medicine at Rockford, Rockford, IL,
USA, 2013.
11.
Top 20 article in relevant field of lung cancer: Puri N, Salgia R. Synergism of EGFR and c-Met
pathways, cross-talk and inhibition, in non-small cell lung cancer. J Carcinogenesis 2008; 7:9-16.
According to BioMedLib in 2013.
12.
Top 10 most downloaded Cancer Treatment Review Article: Ruden M, Puri N. Novel anticancer
therapeutics targeting telomerase. Cancer Treatment Reviews Epub 2012; 39:444-56
doi:10.1016/j.ctrv.2012.06.007. According to Science Direct in 2013.
13.
Research Mentor Award, from Masters in Medical Biotechnology Program, University of Illinois
College of Medicine at Rockford, Rockford, IL, USA, 2014
C. Selected Peer-reviewed Publications
1.
Puri N, Mojamdar M, Ramaiah A. In vitro growth characteristics of melanocytes obtained from adult
normal and vitiligo subjects. J Invest Dermatol. 1987 Apr; 88(4): 434-8. PMID3559270.
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Puri N, Mojamdar M, Ramaiah A. Growth defects of melanocytes in culture from vitiligo subjects are
spontaneously corrected in vivo in repigmenting subjects and can be partially corrected by the addition
of fibroblast-derived growth factors in vitro. Arch Dermatol Res. 1989; 281(3): 178-84. PMID2774645.
Bhatnagar V, Anjaiah S, Puri N, Darshanam BN, Ramaiah A. pH of melanosomes of B 16 murine
melanoma is acidic: Its physiological importance in the regulation of melanin biosynthesis. Arch
Biochem Biophys. 1993 Nov 15; 307(1): 183-92. PMID8239655.
Puri N, van der Weel MB, de Wit FS, Asghar SS, Das PK, Ramaiah A, et al. Basic fibroblast growth
factor promotes melanin synthesis by melanocytes. Arch Dermatol Res. 1996 Sep; 288(10): 633-5.
PMID8919049.
Gardner JM, Wildenberg SC, Keiper NM, Novak EK, Rusiniak ME, Swank RT, et al. The mouse pale
ear (ep) mutation is the homologue of human hermansky-pudlak syndrome. Proc Natl Acad Sci U S A.
1997 Aug 19; 94(17): 9238-43. PMID9256466.
Lund PM, Puri N, Durham-Pierre D, King RA, Brilliant MH. Oculocutaneous albinism in an isolated
tonga community in zimbabwe. J Med Genet. 1997 Sep; 34(9): 733-5. PMID9321758.
Puri N, Durbam-Pierre D, Aquaron R, Lund PM, King RA, Brilliant MH. Type 2 oculocutaneous albinism
(OCA2) in zimbabwe and cameroon: Distribution of the 2.7-kb deletion allele of the P gene. Hum
Genet. 1997 Oct; 100(5-6): 651-6. PMID9341887.
Puri N, Gardner JM, Brilliant MH. Aberrant pH of melanosomes in pink-eyed dilution (p) mutant
melanocytes. J Invest Dermatol. 2000 Oct; 115(4): 607-13. PMID10998131.
Eller MS, Puri N, Hadshiew IM, Venna SS, Gilchrest BA. Induction of apoptosis by telomere 3'
overhang-specific DNA. Exp Cell Res. 2002 Jun 10; 276(2): 185-93. PMID12027448.
Eller MS, Li GZ, Firoozabadi R, Puri N, Gilchrest BA. Induction of a p95/Nbs1-mediated S phase
checkpoint by telomere 3' overhang specific DNA. FASEB J. 2003 Feb; 17(2): 152-62. PMID12554694.
Puri N, Eller MS, Byers HR, Dykstra S, Kubera J, Gilchrest BA. Telomere-based DNA damage
responses: A new approach to melanoma. FASEB J. 2004 Sep; 18(12): 1373-81. PMID15333580.
Puri N, Ahmed S, Janamanchi V, Tretiakova M, Zumba O, Krausz T, et al. c-Met is a potentially new
therapeutic target for treatment of human melanoma. Clin Cancer Res. 2007 Apr 1; 13(7): 2246-53.
PMID17404109.
Puri N, Khramtsov A, Ahmed S, Nallasura V, Hetzel JT, Jagadeeswaran R, et al. A selective small
molecule inhibitor of c-met, PHA665752, inhibits tumorigenicity and angiogenesis in mouse lung cancer
xenografts. Cancer Res. 2007 Apr 15; 67(8): 3529-34. PMID17440059.
Puri N, Salgia R. Synergism of EGFR and c-Met pathways, cross-talk and inhibition, in non-small cell
lung cancer. J Carcinog. 2008; 7: 9. PMID19240370.
Pitman RT, Fong JT, Billman P, Puri N. Knockdown of the fat mass and obesity gene disrupts cellular
energy balance in a cell-type specific manner. PLoS One. 2012; 7:e38444. doi:
10.1371/journal.pone.0038444. PMID22675562.
Ruden M, Puri N. Novel anticancer therapeutics targeting telomerase. Cancer Treat Rev. 2013 Aug;
39(5): 444-56. doi: 10.1016/j.ctrv.2012.06.007. PMID22841437.
Pitman RT, Wojdyla L, Puri N. Mechanism of DNA damage responses induced by exposure to an
oligonucleotide homologous to the telomere overhang in melanoma. Oncotarget. 2013 May; 4(5): 76171. PMID23800953.
Pitman RT, Fong JT, Stone AL, Devito JT, Puri N. FTO knockdown decreases phosphorylation of Tau
in neuronal cells: a potential model implicating the association of FTO with Alzheimer’s disease. J
Alzheimers Dis Parkinsonism. 2013; 3: 125. doi: 10.4172/2161-0460.1000125.
Bertram C, Wojdyla L, Uppada SB, Shearrow C, Botting GM, Rios Z, Puri N. Therapeutic potential of Toligo and its mechanism of action. Metabolomics. 2013; 3:125. doi: 10.4172/2153-0769.1000125.
Fong JT, Jacobs RJ, Moravec DN, Uppada SB, Botting GM, Nlend M, Puri N. Alternative signaling
pathways as potential therapeutic targets for overcoming EGFR/c-Met inhibitor resistance in non-small
cell lung cancer. PLoS One. 2013 Nov 4; 8(11): e78398. doi: 10.1371/journal.pone.0078398.
PMID24223799.
Mulnix RE, Pitman RT, Retzer A, Bertram C, Arasi K, Crees Z, Girard J, Uppada SB, Stone AL, Puri N.
hnRNP C1/C2 and Pur-beta proteins mediate induction of senescence by oligonucleotides homologous
to the telomere overhang. Onco Targets Ther. 2013; Dec 18; 7: 23-32. PMID24379680.
Puri N, Girard J. Novel therapeutics targeting telomerase and telomeres. J Cancer Sci Ther. 2013; 5:
e127. doi:10.4172/1948-5956.1000e127.
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Puri N, Pitman RT, Mulnix RE, Erickson T, Iness AN, Vitali C, Zhao Y, Salgia R. Non-small cell lung
cancer is susceptible to induction of DNA damage responses and inhibition of angiogenesis by
telomere overhang oligonucleotides. Cancer Lett. 2014 Feb 1; 343(1):14-23. PMID24041868.
Uppada SB, Erickson T, Wojdyla L, Moravec DN, Song Z, Cheng J, Puri N. A novel delivery system for
T-oligo using a nanocomplex formed with an alpha helical peptide for melanoma therapy. Int J
Nanomedicine. 2014; 9:43-53. PMID24391441.
Wojdyla L, Stone AL, Sethakorn N, Uppada SB, Devito JT, Bissonnette M, Puri N. T-oligo as an
anticancer agent in colorectal cancer. Biochem Biophys Res Commun. 2014 Apr 4; 446(2):596-601.
PMID: 24632202.
Crees Z, Girard J, Rios Z, Botting GM, Harrington K, Shearrow C, Wojdyla L, Stone AL, Uppada SB,
Devito JT, Puri N. Oligonucleotides and G-quadruplex Stabilizers: Targeting Telomeres and
Telomerase in Cancer Therapy. Curr Pharm Des. 2014 Jun 29. [Epub ahead of print] PMID: 24975605.
Etnyre D, Stone AL, Fong JT, Jacobs RJ, Uppada SB, Botting GM, Rajanna S, Moravec DN,
Shambannagari MR, Crees Z, Girard J, Bertram C, Puri N. Targeting c-Met in melanoma: Mechanism
of resistance and efficacy of novel combinatorial inhibitor therapy. Cancer Biol Ther. 2014 Sep 1;
15(9):1129-41. PMID: 24914950.
Rastogi I, Rajanna S, Puri N. Current Molecularly Targeted Therapies against EGFR for Cancer. J
Cancer Sci Ther. 2014; 6:e131. doi: 10.4172/1948-5956.1000e131.
Stone A, Harrington K, Frakes M, Blank K, Rajanna S, Rastogi I, Puri N. EGFR and c-Met Inhibitors are
Effective in Reducing Tumorigenicity in Cancer. J Carcinog Mutagen. 2014; 5: 173. doi:10.4172/21572518.1000173.
Stone A, Rajanna S, Rastogi I, Cruz J, Harrington K, Blank K, Frakes M, Puri N. c-Met: A Potential
Target for Current Non-Small-Cell Lung Cancer Therapeutics. Chemotherapy. 2014; 3: 136.
doi:10.4172/2167-7700.1000136.
D. Research Support
Current
NIH R21
09/06/2012 – 08/31/2015
Role: PI
“Synergism of c-Met and EGFR pathways: their therapeutic role in lung cancer”
The goal of this study was to determine the role of EGFR and c-Met expression in lung cancer tumorigenicity.
No overlap with the proposed project.
Completed
Pilot grant from the UIC cancer center
01/01/11-12/31/12
Role: PI
“Mechanism of Action and Role of Nano-Assembled Structures as a Drug Delivery System for Novel
Therapeutic Agent T-oligo”.
The goal of this study was the synthesis and in vitro evaluation of nanoparticles containing oligonucleotides
complexed with positively charged, helical polypeptides to study the accumulation of T-oligo containing
nanoparticles in tumors.
UIC Cancer Center Pilot Grant
07/01/09-06/30/11
Role: PI
“c-Met: a Potentially New Therapeutic Target for Treatment of Human Melanoma”.
The goal of this investigation was to determine novel c-Met mutations, their biological significance and function
in human melanoma and determine the efficacy of a potent c-Met inhibitor, SU11274, on tumorigenicity,
metastasis, and angiogenesis of melanoma xenografts.
The Skin Cancer Foundation
03/15/09-3/14/10
Role: PI
Patricia Wexler Research Grant
“T-oligo as a Novel Therapeutic Agent for Melanoma”.
The goal of this investigation was to examine the effects of T-oligo on apoptosis and differentiation in
melanoma cells.
American Cancer Society
08/1/07-7/31/09
Role: PI
“The Telomere 3' Overhang Specific DNA induces Apoptosis and Senescence in Cancer cells in Vitro and
Reduces their Tumorigenicity and Metastasis in Vivo”.
The goal of this investigation was to determine if T-oligo can be used as a therapeutic model to treat
melanoma and lung cancer by studying the effect of T-oligo on animal model systems of melanoma and lung
cancer.
5 R03 AR050110 (Puri) NIH/NIAMSD
07/15/03-6/30/07
Role: PI
“The Effect of Telomere 3' Overhang DNA on Melanoma”.
The goal of this project was to study the role of proapoptotic proteins p73, E2F1 and Rb on T-oligo mediated
apoptosis. Study the effect of T-oligo on differentiation proteins and livin expression and study the effect of Toligo on tumorigenecity of melanoma in SCID mice.