PHS 398/2590 - Cardiovascular Research Training Program

CURRICULUM VITAE
Mazhar ADLI, Ph.D.
Assistant professor
University of Virginia, School of Medicine
Department of Biochemistry and Molecular Genetics
www.adlilab.org
Cell: 919-360-8327
Office: 434-243-8567
Email: [email protected]
Address: 1340 Jefferson Park Ave
Charlottesville, VA, 22908
EDUCATION
Postdoctoral Training, Epigenomics…………………………..……………………………………………2007-2012
Broad Institute and Massachusetts General Hospital, Harvard Medical School
Advisor: Prof. Bradley E. Bernstein
Ph.D., Molecular Biology………………………………………………………………………………..……2002-2007
The University of North Carolina at Chapel Hill, NC, USA
Advisor: Prof. Albert S. Baldwin
M.Sc., Biological Sciences and Bioengineering….……………………………………………..…………….2000-2002
Sabanci University, Istanbul, Turkey
Advisor: Prof. Huveyda Basaga
B.S., Molecular Biology…………………………………………………...………………………..…………1995-2000
Middle East Technical University, Ankara, Turkey
B.A., Science Education……………………………………………………...………………………..………1995-2000
Middle East Technical University, Ankara, Turkey
PROFESSIONAL POSITIONS
Assistant Professor (tenure-track)…………………..……………...…………………………………09/2012-Present
University of Virginia, School of Medicine, Department of Biochemistry and Molecular Genetics
Active Member, American Association of Cancer Research (AACR)…………….....................................2016-Present
Member, faculty search committee, UVA department of Biochemistry..……………….................................2014-2015
Member, Grant review committee, Welcome Trust, UK………...…………………………..…………..……2015
Member, NASA International Life Sciences Research grant review panel ……..…...………………………2014
Member, NIH/ NIEHS review panel, TaRGET I (R01)...…………………...………………….………… March, 2013
Founding Member, Boston Biologist Colloquium of Harvard Medical School.……..…....……...…...… 2011-Present
Postdoctoral Research Fellow……………………..………………...………………………….…….09/2007-08/2012
Harvard Medical School, Massachusetts General Hospital, Broad Institute
Research Assistant.……………….……………………………..……...………………………………….....2002-2007
The University of North Carolina at Chapel Hill, Department of Biology, NC, USA
Research Assistant.……………….……………………………….…………........……………………….....2000-2002
Sabanci University, Istanbul, Turkey
HONORS & AWARDS
V Scholar plus award, V foundation for cancer research.…….……….….................................................2016-present
V Scholar, V foundation for cancer research.…….……….…......................................……………...............2014-2016
STARR Cancer Consortium Visiting Fellow Award….…..…….……….…...……………...............…………...2011
Sabanci Scholarship (Tuition and Stipend)….…………….……………...…………………..............……...2000-2002
Sabanci University, Istanbul, Turkey
President’s High Honor Graduate Award (Ranked 1st in the Graduate School)…...……………………….........2002
Graduate School of Biological Sciences and Bioengineering, Sabanci University, Istanbul, Turkey
Presidential-METU Scholarship (tuition and stipend) …...…………………………...…………………….1995-2000
Middle East Technical University, Ankara, Turkey
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President’s Honor Student Award (both in Major and Double Major Programs)………..…...……………1995-2000
Middle East Technical University, Ankara, Turkey
PUBLICATIONS
Published Articles:
1. Kuscu, Parlak M, Tufan T, Yanh J, Szlachta K, Mammeadov R, Adli M. CRISPR-STOP: Gene silencing
through base editer-induced nonsense mutations
Nature Methods, 2017 (January 2017, accepted in principle)
2. Peiwu Q*, Parlak M*, Kuscu C, Bandaria J, Singh R, Yildiz A & Adli M. Multicolor labeling and imaging
nuclear organization of native chromatin loci with type II CRISPR/Cas9 system in living cells.
Nature Communication, 2017
* Equally Contributed
3. Kuscu C & Adli M. CRISPR/Cas9-AID base editor is a powerful gain of function screening tool.
Nature Methods, 2016. DOI: 10.1038/nmeth.4076.
4. Ataman B, Boulting GL, Harmin DA, Yang MG, Baker-Salisbury M, Yap EL, Malik AN, Mei K, Rubin AA,
Spiegel I, Durresi E, Sharma N, Hu LS, Pletikos M, Griffith EC, Partlow JN, Stevens CR, Adli M, Chahrour
M, Sestan N, Walsh CA, Berezovskii VK, Livingstone MS, Greenberg ME. 1. Evolution of Osteocrin as an
activity-regulated factor in the primate brain.
Nature, 2016. DOI: 10.1038/nature20111.
5. Illendula N, Gilmour J, Grembecka J, Tirumala V.S.S, Boulton A, Kuntimaddi A, Schmidt C, Wang L,
Pulikkan JA, Zong H, Parlak P, Kuscu C, Pickin A, Zhou Y, Gao Y, Mishra L, Adli M, Castilla LH, Rajewski
RA, Janes KA, Guzman ML, Bonifer C, Bushweller JH. Small Molecule Inhibitor of CBFβ-RUNX Binding for
RUNX Transcription Factor Driven Cancers.
EBioMedicine, 2016. DOI: http://dx.doi.org/10.1016/j.ebiom.2016.04.032
6. Anderson CJ, Clark DE, Adli M, Kendall MM. Ethanolamine Signaling Promotes Salmonella Niche
Recognition and Adaptation during Infection.
PLoS Pathogen, 2015. DOI: 10.1371/journal.ppat.1005278.
7. Singh R, Kuscu C, Quinlan A, Qi Y & Adli M, Cas9-Chromatin binding information enables more accurate
CRISPR Off-target Prediction.
Nucleic Acid Research, 2015. DOI: 10.1093/nar/gkv575.
8. Kuntimaddi A, Achille NJ, Thorpe J, Lokken AA, Singh R, Hemenway CS, Adli M, Zeleznik-Le NJ,
Bushweller JH. Degree of Recruitment of DOT1L to MLL-AF9 Defines Level of H3K79 Di- and Trimethylation on Target Genes and Transformation Potential.
Cell Reports, 2015. DOI: 10.1016/j.celrep.2015.04.004.
9. Roadmap Epigenomics Consortium. Integrative analysis of 111 reference human epigenomes.
Nature, 2015. DOI: 10.1038/nature14248.
10. Qin F, Song Z, Babiceanu M, Song Y, Facemire L, Singh R, Adli M& Li H. Discovery of CTCF-sensitive
cis-spliced fusion RNAs between adjacent genes in human prostate cells.
PloS Genetics, 2015. DOI: 10.1371/journal.pgen.1005001.
11. Adli M, Parlak M, Li Y, El-Dahr S. Epigenetic States of Nephron Progenitors and Epithelial Differentiation.
J Cell Biochem, 2015. DOI: 10.1002/jcb.25048.
12. Rubeis et al.(Adli M: consortium collaborator). Synaptic, transcriptional and chromatin genes disrupted in
autism.
Nature, 2014. DOI: 10.1038/nature13772.
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13. Kuscu C, Arslan S, Singh R, Thorpe J, Adli M. Genome-wide analysis reveals characteristics of off-target
sites bound by the Cas9 endonuclease.
Nature Biotechnology, 2014. DOI: 10.1038/nbt.2916.
14. Rissman EF, Adli M. Transgenerational epigenetic inheritance: focus on endocrine disrupting compounds.
Endocrinology, 2014. DOI: 10.1210/en.2014-1123.
15. Abdel-Wahab O*, Gao j*, Adli M*, Dey A, Trimarchi T, Rock Chung RY, Kuscu C, Hricik T, Lobry ND, La
Fave L, Koche R, Shih AH, Guryanova OA, Pandey S, Shin Y, Bhatt PK, Monette S, Taylor JE, Zhao X,
Jaffe JD, Dixit V, Park CY, Bernstein BE, Aifantis I, and Levine RL. Deletion of Asxl1 Results in
Myelodysplasia and Severe Developmental Defects in Vivo.
Journal of Experimental Medicine, 2013. DOI: 10.1084/jem.20131141, PMCID: PMC3832937.
*Equally contributed
16. Zhu J* & Adli M*#, Zou J, Verstappen G, Coyne M, Zhang X, Durham T, Miri M, Deshpande V, De Jager
PL, Bennett DA, Houmard JA, Muoio DM, Onder TT, Camahort R, Cowan C, Meissner A, Epstein CB,
Shoresh N and Bernstein BE#. Genome-wide chromatin state transitions associated with developmental
and environmental cues.
Cell, 2013. DOI: 10.1016/j.cell.2012.12.033 PMCID: PMC3563935.
*Equally contributed, #Co-corresponding author.
17. T.W. Yu, M.H. Chahrour, M.E. Coulter, S. Jiralerspong, K. Okamura-Ikeda, B. Ataman, D.A. Harmin, Adli
M, A.N. Malik, A. D'Gama, K. Schmitz-Abe, E. Lim, S.J. Sanders, G.H. Mochida, J.N. Partlow, C.M. Sunu,
J.M. Felie, J. Rodriguez, J. Ware, R.M. Joseph, R.S. Hill, B.Y. Kwan, M. Al-Saffar, N.M. Mukaddes, A.
Hashmi, S. Balkhy, G.G. Gascon, F.M. Hisama, E. LeClair, A. Poduri, O. Oner, S. Al-Saad, T. Ben-Omran,
L. Al-Gazali, V. Eapen, C.R. Stevens, L. Rappaport, S.B. Gabriel, K. Markianos, M.W. State, M.E.
Greenberg, H. Taniguchi, N.E. Braverman, E.M. Morrow, C.A. Walsh. Using whole exome sequencing to
identify inherited causes of autism.
Neuron, 2013. DOI: 10.1016/j.neuron.2012, PMCID: PMC3694430.
18. AbdelWahab O*, Adli M*, LaFave LM, Gao J, Hricik T, Shih AH, Pandey S, Patel JP, Chung YR, Koche R,
Perna F, Zhao X, Taylor JE, Park CY, Carroll M, Melnick A, Nimer SD, Jaffe JD, Aifantis I, Bernstein BE,
Levine RL. ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene
repression.
Cancer Cell. 2012. DOI: 10.1016/j.ccr.2012.06.032, PMCID: PMC3422511.
*Equally contributed
19. Adli M, Bernstein BE. Whole-genome chromatin profiling from limited numbers of cells using nano-ChIPseq.
Nature Protocols, 2011. DOI: 10.1038/nprot.2011.402. NIHMSID: NIHMS427239.
20. Adli M, Zhu J, Bernstein BE. Genome-wide chromatin maps derived from limited numbers of hematopoietic
progenitors.
Nature Methods. 2010. DOI: 10.1038/nmeth.1478, PMCID: PMC2924612.
21. Goren A, Ozsolak F, Shoresh N, Ku M, Adli M, Hart C, Gymrek M, Zuk O, Regev A, Milos PM, Bernstein
BE. Chromatin profiling by directly sequencing small quantities of immunoprecipitated DNA.
Nature Methods, 2010. DOI: 10.1038/nmeth.1404, PMCID: PMC2862482.
22. Ku M, Koche RP, Rheinbay E, Mendenhall EM, Endoh M, Mikkelsen TS, Presser A, Nusbaum C, Xie X,
Chi AS, Adli M, Kasif S, Ptaszek LM, Cowan CA, Lander ES, Koseki H, Bernstein BE. Genome-wide
analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains.
PLoS Genetics, 2008. DOI: 10.1371/journal.pgen.1000242, PMCID: PMC2567431.
23. Koppikar P, Bhagwat N, Kilpivaara O, Manshouri T, Adli M, Hricik T, Liu F, Saunders LM, Mullally A,
Abdel-Wahab O, Leung L, Weinstein A, Marubayashi S, Goel A, Gönen M, Estrov Z, Ebert BL, Chiosis G,
Nimer SD, Bernstein BE, Verstovsek S, Levine RL. Heterodimeric JAK-STAT activation as a mechanism of
persistence to JAK2 inhibitor therapy.
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Nature, 2012. DOI: 10.1038/nature11303, PMCID: PMC3991463.
24. Chapman MA, Lawrence MS, Keats JJ, Cibulskis K, Sougnez C, Schinzel AC, Harview CL, Brunet JP,
Ahmann GJ, Adli M, Anderson KC, Ardlie KG, Auclair D, Baker A, Bergsagel PL, Bernstein BE, Drier Y,
Fonseca R, Gabriel SB, Hofmeister CC, Jagannath S, Jakubowiak AJ, Krishnan A, Levy J, Liefeld T, Lonial
S, Mahan S, Mfuko B, Monti S, Perkins LM, Onofrio R, Pugh TJ, Rajkumar SV, Ramos AH, Siegel DS,
Sivachenko A, Stewart AK, Trudel S, Vij R, Voet D, Winckler W, Zimmerman T, Carpten J, Trent J, Hahn
WC, Garraway LA, Meyerson M, Lander ES, Getz G, Golub TR. Initial genome sequencing and analysis of
multiple myeloma.
Nature, 2011. DOI: 10.1038/nature09837, PMCID: PMC3560292.
25. Koche RP, Smith ZD, Adli M, Gu H, Ku M, Gnirke A, Bernstein BE, Meissner A. Reprogramming factor
expression initiates widespread targeted chromatin remodeling.
Cell Stem Cell. 2011. DOI: 10.1016/j.stem.2010.12.001, PMCID: PMC3220622.
26. Adli M, Merkhofer E, Cogswell P, Baldwin AS. IKKalpha and IKKbeta each function to regulate NF-kappaB
activation in the TNF-induced/canonical pathway.
PLoS One, 2010. DOI:10.1371/journal.pone.0009428. PMCID: PMC2828475.
27. Dan HC, Adli M, Baldwin AS. Regulation of mammalian target of rapamycin activity in PTEN-inactive
prostate cancer cells by I kappa B kinase alpha.
Cancer Research, 2007. PMID: 17616684.
28. Adli M, Baldwin AS. IKK-i/IKKepsilon controls constitutive, cancer cell-associated NF-kappaB activity via
regulation of Ser-536 p65/RelA phosphorylation.
Journal of Biological Chemistry. 2006 Sep 15;281(37):26976-84. PMID: 16840782.
29. Kutuk O, Adli M, Poli G, Basaga H. (2004). Resveratrol protects against 4-HNE induced oxidative stress
and apoptosis in Swiss 3T3 fibroblasts.
Biofactors. 2004; 20(1):1-10. PMID: 15096656.
PATENTS
1. Adli M. Using in vivo CRISPR screening viability scores to predict therapeutic response of cancer drugs
(Application submitted, September 2016)
2. Adli M, Mikkelsen T, Bernstein BE. Methods for preparing high throughput sequencing libraries from scarce amount
of DNA. Patent #: USA, 12/699,508
RESEARCH SUPPORT
GF13102
Adli (PI)
01/10/14 – 09/30/16
The V Foundation for Cancer Research
Epigenetic Engineering to Correct an Aberrantly Regulated Locus in Cancer
The goal of this study is to use novel epigenetic engineering tools to change and reprogram aberrant chromatin
state and function at specifically targeted genomic regions.
Role: PI
5 R01ES022759-02
Rissman (PI)
06/15/14 – 02/28/19
NIH/NIEHS
Transgenerational actions of the endocrine disrupting compound Bisphenol A
The aim is to determine the parent of origin and mechanisms by which Bisphenol A has transgenerational
actions on gene expression and behavior.
Role: Co-Investigator
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Completed Research Support
5 P50 DK096373-03
Gomez (PI)
09/01/14 – 08/31/15
NIH/NIDDK
Kidney development cell fate and precursors of disease in the young and adult
Pilot Project: CRISPR mediated whole-genome knock-out screening to identify essential genes in
nephrovascular development
The aim of this Pilot Project is to target every single gene in the genome by more than 10 unique sgRNAs to
achieve CRISPR/Cas9 mediated genetic knock-outs. This will allow identification of essential genes for a
specific cellular phenotype; the genes that are positively or negatively regulating a given phenotype or a cellular
state.
Role: PI (Pilot Project)
CaTS Pilot Project
Adli (PI)
11/01/14 – 10/31/15
UVA Cancer Center & NCI CCSG P30 CA44579
In vivo CRISPR based knock-out screening to identify essential epigenetic regulators of tumor progression in
xenograft model of pancreatic cancer
The aim of this project is to use CRISPR gene editing technology to perform knock screenings to identify
essential genes involved in in vivo tumor progression and chemotherapy resitance in PDAC.
Role: PI
CaTS Pilot Project
Zhong & Adli (co-PI)
11/01/14
–
10/31/15
UVA Cancer Center & NCI CCSG P30 CA44579
Targeting Radiation Resistance in Glioma
The aim of this project is to identify the mechanism of radioresistance glioblastoma. The Adli lab will perform
an unbiased genome-wide CRISPR gene knock-out screening to identify essential genes responsible for
radioresistance.
Role: Co-PI
ACS-IGR
Adli (PI)
11/2012 – 11/2013
American Cancer Society Institutional Research Grant
Characterizing genomic targets and epigenetic aberrations due to ASXL1 and EZH2 mutations in myeloid
malignancies
Role: PI
Pending Research Support:
1R01 CA211648-01 (2 percentile score)
Adli (PI)
01/17–12/20
NIH/NCI
$323,201
Title: Identifying the Drivers and Targeting Chemo Resistance in Ovarian Cancer
The overall goal of our research has focused on understanding the genetic and epigenetic basis of chemoresistance in ovarian cancer. Our in preliminary results suggest that aberrant regulation at specific sets of distal
regulatory sites in the genome called super enhancers drive the chemo resistance in ovarian cancer. We
hypothesize that the development of chemoresistance in ovarian cancer is mediated, at least partially, by
epigenetic alterations at these regulatory genomic elements. The overarching goal of this proposal is to
characterize the functional roles of these elements in vivo and characterize the role of genes that are targets of
these elements.
1R01CA215713-01 (22 percentile, 1st submission, resubmitted)
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Adli (PI)
04/17-03/22
NIH/NCI
$312,701
Title: Identifying novel drug targets in pancreatic cancer through in vivo screening
We are presenting evidence that genome-scale genetic knockout (KO) screenings in in vivo propagated, patientderived tumors can be used to identify novel drug targets for pancreatic cancer. We have already demonstrated
the power of this approach in our preliminary results. In this proposal, we will validate our preliminary findings
and perform additional screenings to identify novel drug targets, which can be utilized to enhance the
therapeutic response of standard of care chemotherapy agents for pancreatic cancer.
INVITED TALKS
(National and International)
1. Temporal and spatial epigenome editing allows precise gene regulation
41st Federation of European Biochemical Societies (FEBS), 2016, Izmir, TURKEY
2. Manipulating Chromatin structure and function
Molecular Biology Association of Turkey, 2016, Denizli, TURKEY
3. Dual labeling and imaging chromatin structure using CRISPR technology
Biological and clinical frontiers in epigenetic, Epicypher 2016, San Juan, PUERTO RICO
4. Understanding and manipulating human epigenome
Turkish biochemical society annual meeting, 2015, Antalya, TURKEY
5. How to perform and publish high impact science.
Turkish biochemical society annual meeting, 2015, Antalya, TURKEY
6. Using CRISPR to do locus specific epigenome editing and chromatin visualization
Gordon Research Conference, Cell Growth & Proliferation, 2015, Mount Snow, VT, USA
7. Understanding the CRISPR targeting specificity
Functional Genomics & Predictive Medicine, Boston, MA, USA, May 2015
8. Understanding and manipulating human epigenome
Memorial Sloan Kettering Cancer Center, HOPP, New York, NY, USA March 2015
9. Understanding and manipulating human epigenome
East Carolina University, Grenville, NC, USA April 2015
10. Understanding and manipulating human epigenome
Koc University, Istanbul, Turkey, Nov 2014
11. Understanding and manipulating human epigenome
Sabanci University, Istanbul, Turkey, Nov 2014
12. Understanding and manipulating human epigenome
Bogazici University, Istanbul, Turkey, Nov 2014
13. Whole genome analysis of CRISPR/Ca9 targeting specificity
FASEB Genome Engineering meeting, Nassau, Bahamas, June 2014
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14. Manipulating the human epigenome with CRISPR technology
National Institute of Health, NCI, Bethesda, MD, USA, May 2014
15. Understanding Human Epigenome
University of Virginia, Center for Public Health Genomic, Charlottesville, VA, USA, November 2013
16. Comparative analysis of human epigenomic maps
Epigenomics: A Roadmap to the Living Genome Meeting (NIH), Boston, USA October 2013
17. Chromatin state transition in response to developmental and environmental cues.
World Epigenetics Summit, Boston, USA, July 2013
18. Human epigenome in normal and malignant settings
13th International Stroke Genetics Consortium, Charlottesville, VA, April, 2013
19. Large scale chromatin and cellular state transitions
University of Virginia, School of Medicine, January 2013
20. Understanding human epigenome
University of Chicago, Chicago, IL, March 2012
21. Whole genome mapping of human epigenome
University of California at Riverside. Riverside, CA, February 2012
22. Human epigenome reveals dynamics of cellular state transitions
Arizona state university, Phoenix, AZ, January, 2012
23. Understanding the whole genome mapping of human epigenome
University of Wisconsin at Madison, Madison, WI, December 2011
24. Epigenomic landscape of primary and ex vivo expanded hematopoietic stem cells
Fred Hutchinson Cancer Research Center, Seattle, WA, USA, September 2010
25. Epigenomic landscape in hematopoietic development
Koc University, Istanbul, Turkey, January 2010
26. Large-scale epigenomic studies in hematopoietic development and disease
Sabanci University, Istanbul, Turkey, January 2010
27. Genome-wide maps of protein-DNA interactions by high throughput DNA sequencing
Health, Science and Technology Workshop, Bosphorus University, Istanbul, Turkey, December 2009
28. Large-Scale Studies of the Epigenetics of Human Leukemia
STARR Cancer consortium, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY, USA, September 2009
29. Epigenomic landscape in hematopoietic development and disease
Cancer Genomics Platform, Broad Institute, Cambridge, MA, USA, November 2009
30. Genome-wide chromatin state analysis of pluripotent and multi-potent stem cells
MGH Cancer Center, MGH Navy Yard, Boston, MA, USA, October 2009
TEACHING EXPERIENCE
Chromatin II (BIOC814): Cancer Epigenetics…….……………………………....………….……....….………2016
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Chromatin II (BIOC814): Epigenome Editing…….………………………………………….…….....…………2016
PHS5500: Genome editing technologies…….………………………………...……………….…….....…………2016
BIMS Core Course, Genome editing technologies…….………………………………...…….……....…………2015
SoM, Foundations of Molecular Medicine, Molecular Medicine Techniques…….………………..………..…2015
BIMS Core Course, Nucleosome remodeling…….…………………...…………………………..………...……2015
SoM, Foundations of Molecular Medicine, Molecular Medicine Techniques…….………….….…………..…2015
BIMS Core Course, Genome editing technologies…….…………………...…………………..………...………2014
Teaching assistant (Introduction to Genetics).…………….………………….……...………………...…….2003-2004
The University of North Carolina at Chapel Hill, Department of Biology
Teaching assistant (Natural Sciences 101: Introduction to Biology).……………..……………………...….2001-2002
Sabanci University, Biological Sciences and Bioengineering Program, Istanbul, Turkey
Substitute high school biology teacher…….……………………………………………………..……...….1999-2000
Private Ari High School, Ankara, Turkey
MENTORING EXPERIENCE:
Postdoctoral fellows:
1. Cem Kuscu
2. Jiekun Yang
3. Tom Xiaolong
4. Karol Szlachta
5. Sevki Arslan
6. Mahmut Parlak
7. Rashad MemMedow
PhD committees:
1. Stephen Sang (PI: Mazhar Adli)
2. Ritambhara Singh (co-PI: Mazhar Adli)
3. Steve Griffith (PI: Gary Owens)
4. Charles Goforth (PI: Gary Owens)
5. Magdalena Cichewicz (PI: Anindya Dutta)
6. Bruno Takao (PI: Anindya Dutta)
7. Brian Reon (PI: Anindya Dutta)
8. Peter Balogh (PI: Adem Goldfarb)
9. Luke Oosdyk (Bryce Paschal)
10. Erin Harris (PI: Emilie Rissman)
11. Gabriel Falco Alencar (PI: Gary Owens)
12. Aravinda Kuntimaddi (PI: John Bushweller)
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