Jianjun Chen, Ph.D.

APPOINTMENTS

  • Assistant Professor, Department of Medicine, Section of Hematology/Oncology, Committee on Cancer Biology, Cancer Research Center

EDUCATION

Ph.D., Shanghai Institute of Biochemistry, Chinese Academy of Sciences, Shanghai, China, 1999

CONTACT INFORMATION

The University of Chicago
KCBD 7134 
900 East 57th Street
Chicago, Illinois 60637

jchen@medicine.bsd.uchicago.edu

Phone:  (773) 834-2459

RESEARCH SUMMARY

Integrated analyses of cancer-“omics”; microRNAs and target genes in leukemias, lymphomas, normal hematopoiesis and embryonic stem cells; Cancer stem cells and drug resistance; Natural antisense RNAs.

As a cancer research scientist, I believe that the advance of basic cancer research will bring novel insights into the pathology of diseases and may result in new therapy methods for treatment of diseases. My ultimate career goal is to become a leader in academic medicine, particularly in the field of Hematology-Oncology, by developing a deep understanding of cancer biology, and by bringing that knowledge to the benefit of patients through collaboration with clinical colleagues.

LONG-TERM RESEARCH GOALS:
Integrated analyses of cancer-“omics”: Cancer is a complex disease involving multiple steps in development which include initiation, promotion, malignant conversion, progression, and metastasis. In normal cells, gene expression is tightly regulated by complex networks which consist of both protein-coding and non(-protein)-coding genes (e.g., microRNAs and antisense RNAs). The disruption of such regulatory networks by genetic and/or epigenetic changes could lead to the development of cancer. Genetic changes can include sequence mutation, gene deletion, and loss of heterozygosity (LOH). Epigenetic changes may include DNA methylation and histone modifications. The complexity in tumorigenesis is due to huge diversities of the genetic and epigenetic aberrations and the numerous associated molecular networks. Therefore, integrated analyses of cancer-“omics” appear to be extremely critical for us to understand the complexity of pathogenetic networks associated with cancer development. My major research interests is to conduct integrated analyses of cancer-“omics” on both protein-coding and non-coding genes regarding both genetic and epigenetic changes in the development of cancers, using various techniques, to obtain a more complete understanding of the complex genetic and epigenetic alterations in cancer development and to identify novel markers and targets for the diagnosis, prognosis prediction, and treatment of cancers.

Cancer stem cells and drug resistance: In many cases, chemotherapy kills most cancer cells and the patients achieve a complete remission; however, the patients relapse after several months or years often with drug resistance. The cancer stem cell hypothesis suggests that a rare fraction of cells with stem cell proprieties, namely cancer stem cells, can survive chemotherapy and support re-growth of tumor, which might be an important mechanism of drug resistance. This hypothesis has received more and more supportive evidence. Stem cells are primal cells that retain the ability to renew themselves through cell division and can differentiate into a wide range of specialized cell types. Cancer stem cells, with either inherent or acquired capabilities for self-renewal, share many properties of the normal stem cells. It is of great importance to conduct our therapy directly against cancer stem cells. However, if we target the shared pathways between cancer and normal stem cells, the therapy against cancer stem cells might also eliminate their normal counterparts. Thus, it is very critical to identify the pathways that differentially impact the self-renewal of normal and cancer stem cells within the same tissue. I plan to employ both genomic and genetic tools to identify cancer-stem-cell-specific genetic and epigenetic changes on both protein-coding and non-coding genes. These genes and the relevant pathways probably could serve as therapeutic targets in the future to overcome the drug resistance problem.

SELECTED PAPERS

Representative papers (selected from around 60)

1)      Chen J, Rowley JD and Wang SM. Generation of longer cDNA fragments from serial analysis of gene expression tags for gene identification. Proc. Natl. Acad. Sci. USA. 2000, 97(1): 349-353.

2)      Chen J, Rowley DA, Clark T, Lee S, Zhou G, Beck C, Rowley JD and Wang SM. The pattern of gene expression in mouse Gr-1+ myeloid progenitor cells. Genomics. 2001, 77(3): 149-162.

3)      Chen J, Lee S, Zhou G and Wang SM. High-throughput GLGI procedure for converting a large number of serial analysis of gene expression tag sequences into 3 complementary DNAs. Genes, Chromosomes & Cancer. 2002, 33(3): 252-261.

4)      Chen J, Sun M, Lee S, Zhou G, Rowley JD and Wang SM. Identifying novel transcripts and novel genes in the human genome by using novel SAGE tags. Proc Natl Acad Sci USA. 2002. 99(19): 12257-12262.

5)      Chen J*, Sun M, Kent WJ, Huang X, Xie H, Wang W, Zhou G, Shi RZ and Rowley JD. Over 20% of human transcripts might form sense-antisense pairs. Nucleic Acids Research. 2004. 32(16):4812-4820.

6)      Chen J*, Sun M, Hurst LD, Carmichael GG and Rowley JD. Human antisense genes have unusually short introns: evidence for selection for rapid transcription. Trends in Genetics. 2005. 21(4): 203-207.

7)      Chen J, Sun M, Hurst LD, Carmichael GG and Rowley JD. Genome-wide analysis of coordinate expression and evolution of human cis-encoded sense-antisense transcripts. Trends in Genetics. 2005. 21(6): 326-329.

8)      Chen J*, Sun M, Rowley JD and Hurst LD. The small introns of antisense genes are better explained by selection for rapid transcription than by ‘genomic design’. Genetics. 2005. 171: 2151-2155.

9)      Sun M, Hurst LD, Carmichael GG and Chen J*. Evidence for a preferential targeting of 3' UTRs by cis-encoded natural antisense transcripts. Nucleic Acids Research. 2005. 33(17): 5533–5543.

10)   Sun M, Hurst LD, Carmichael GG and Chen J*. Evidence for variation in abundance of antisense transcripts between multicellular animals but no relationship between antisense transcriptionand organismic complexity. Genome Research. 2006. 16: 922-933.

11)   Mi S, Lu J, Sun M, Li Z, Zhang H, Neilly MB, Wang Y, Qian Z, Jin J, Zhang Y, Bohlander SK, Le Beau MM, Larson RA, Golub TR, Rowley JD and Chen J*. MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci USA. 2007. 104(50): 19971-19976.

12)   Li Z, Lu J, Sun M,  Mi S, Zhang H, Luo RT, Qian Z, Neilly MB, Wang Y, Jin J, Zhang Y, Bohlander SK, Larson RA, Le Beau MM, Thirman MJ, Golub TR, Rowley JD and Chen J*. Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proc Natl Acad Sci USA. 2008. 105 (40): 15535-15540.

13)   Zhang Z, Li Z, Gao C, Chen P, Chen J, Liu W, Xiao S and Lu H. miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Laboratory Investigation. 2008. 88, 1358–1366.

14)   Li Z, Luo RT, Mi S, Sun M, Chen P, Bao J, Neilly MB, Jayathilaka N, Johnson DS, Wang L, Lavau C, Zhang Y, Tseng C, Zhang X, Wang J, Yu J, Yang Y, Wang SM, Rowley JD, Chen J* and Thirman MJ.  Consistent deregulation of gene expression between human and murine MLL-rearrangement leukemias. Cancer Research. 2009. 69(3):1109-16.

15)   Popovic R, Riesbeck LE, Velu CS, Chaubey A, Zhang J, Achille NJ, Erfurth FE, Eaton K, Lu J, Grimes HL, Chen J, Rowley JD and Zeleznik-Le NJ. Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to leukemia. Blood. 2009. 113(14):3314-22. PMCID: PMC2665896.

16)   Chen J, Odenike O, and Rowley JD. Leukemogenesis: More Than Mutant Genes. Nature Reviews Cancer. 2010. 10(1): 23-36. PMCID: PMC2972637. (Review)

17)   Mi S, Li Z, Chen P, He C, Cao D, Elkahlounb A, Lu J, Huang H, Wunderlich M, Luo RT, Pelloso LA, Sun M, He M, Neilly MB, Zeleznik-Le NJ, Thirman MJ, Mulloy JC, Liu PP, Rowley JD, and Chen J*. Aberrant overexpression and function of the miR-17-92 cluster in MLL-rearranged acute leukemia. Proc Natl Acad Sci USA. 2010. 107(8): 3710-3715.

18)   Wang Y, Li Z, He C, Wang D, Yuan X, Chen J*, Jin J. MicroRNAs expression signatures are associated with lineage and survival in acute leukemias. Blood Cells Mol Dis. 2010. 44(3):191-197. PMCID: PMC2829339

19)   Du W, Li J, Sipple J, Chen J, Pang Q. A cytoplasmic FANCA-FANCC complex interacts and stabilizes the leukemic NPMc protein. J Biol Chem. 2010. 285(48): 37436-37444. PMCID: PMC2988349

20)   Xiong Y, Li Z, Ji M, Tan AC, Bemis J, Tse JV, Huang G, Park J, Ji C, Chen J, Bemis LT, Bunting KD, Tse W. MIR29B regulates expression of MLLT11 (AF1Q), an MLL fusion partner, and low MIR29B expression associates with adverse cytogenetics and poor overall survival in AML. Br J Haematol. 2011. 153(6):753-757. PMCID: pending.

21)   He C, Li Z, Chen P, Huang H, Hurst LD, Chen J*. Young intragenic miRNAs are less coexpressed with host genes than old ones: implications of miRNA-host gene coevolution. Nucleic Acids Res. 2012. 40(9):4002-12. PMCID: PMC3351155.

22)   Li Z, Huang H, Li Y, Jiang X, Chen P, Arnovitz S, Radmacher MD, Maharry K, Elkahloun A, Yang X, He C, He M, Zhang Z, Dohner K, Neilly MB, Price C, Lussier YA, Zhang Y, Larson RA, Le Beau MM, Caligiuri MA, Bullinger L, Valk PJ, Delwel R, Lowenberg B, Liu PP, Marcucci G, Bloomfield CD, Rowley JD, Chen J*. Up-regulation of a HOXA-PBX3 homeobox-gene signature following down-regulation of miR-181 is associated with adverse prognosis in patients with cytogenetically-abnormal AML. Blood. 2012. 119(10):2314-24. PMCID: PMC3311258.

23)   Li Z, Huang H, Chen P, He M, Li Y, Arnovitz S, Zhang J, Hyjek E, Elkahloun A, Jiang X, Zhang Z, He C, Cao D, Shen C, Vardiman J, Wunderlich M, Wang Y, Neilly MB, Jin J, Wei M, Lu J, Molly JC, Zeleznik-Le NJ, Liu PP, Zhang J, Chen J*. miR-196b Directly Targets Both HOXA9/MEIS1 Oncogenes and FAS Tumor Suppressor in MLL-rearranged Leukemia. Nature Communications. 2012. 2:688. PMCID: PMC3514459.

24)   He M, Chen P, Arnovitz S, Li Y, Huang H, Neilly MB, Wei M, Rowley JD, Chen J, Li Z. Two isoforms of HOXA9 function differently but work synergistically in human MLL-rearranged leukemia. Blood Cells Mol Dis. 2012. 49(2):102-6. PMCID: PMC3399022.

25)   Sui X, Price C, Li Z, Chen J*. Crosstalk between DNA and histones: Tet’s new role in embryonic stem cells. Current Genomics. 2012. 13(8): 603-608. PMCID: pending. (Review)

26)   Jiang X, Chen J*. miR-150: targeting MLL leukemia. Oncotarget. 2012. 3(11):1268-9. PMCID: pending. (Review)

27)   Jiang X, Huang H, Li Z,  Li Y, Wang X, Gurbuxani S, Chen P, He C, You D, Zhang S, Wang J, Arnovitz S, Elkahloun A, Price C, Hong GM, Ren H, Kunjamma RB, Neilly MB, Matthews J, Xu M, Larson RA, Le Beau MM, Slany RK, Liu PP, Lu J, Zhang J, He C, Chen J*. Blockade of miR-150 maturation by MLL-fusion/MYC/LIN-28 is required for MLL-associated leukemia. Cancer Cell. 2012. 22: 524-535. PMCID: PMC3480215.

28)   Jiang X, Huang H, Li Z, He C, Li Y, Chen P, Gurbuxani S, Arnovitz S, Hong GM, Price C, Ren H, Kunjamma RB, Neilly MB, Salat J, Wunderlich M, Slany RK, Zhang Y, Larson RA, Le Beau MM, Mulloy JC, Rowley JD, Chen J*. miR-495 is a tumor-suppressor microRNA down-regulated in MLL-rearranged leukemia. Proc Natl Acad Sci USA. 2012. 109(47):19397-402. PMCID: PMC3511140

29)   Li Z, Zhang Z, Li Y, Arnovitz S, Chen P, Huang H, Jiang X, Hong GM, Kunjamma RB, Ren H, He C, Wang CZ, Elkahloun AG, Valk PJM, Dohner K, Neilly MB, Bullinger L, Delwel R, Lowenberg B, Paul P. Liu, Morgan R, Rowley JD, Yuan CS,  Chen J*. PBX3 is an important cofactor of HOXA9 in leukemogenesis. Blood. 2013. 121(8):1422-31. PMCID: PMC3578957.

30)   Li Z, Herold T, He C, Valk PJM, Chen P, Jurinovic V, Mansmann U, Radmacher M, Maharry K, Sun M, Yang X, Huang H, Jiang X, Sauerland MC, Büchner T, Hiddemann W, Elkahloun A, Neilly MB, Zhang Y, Larson RA, Le Beau MM, Caligiuri MA, Dohner K, Bullinger L, Liu PP, Delwel R, Marcucci G, Lowenberg B, Bloomfield CD, Rowley JD, Bohlander SK, Chen J*. Identification of a 24-Gene Prognostic Signature That Improves the European LeukemiaNet Risk Classification of Acute Myeloid Leukemia: An International Collaborative Study of 1,324 Patients. Journal of Clinical Oncology. 2013. 31(9):1172-81. PMCID: PMC3595425.

31)   Sun M, Song CX, Huang H, Frankenberger CA, Sankarasharma D, Gomes S, Chen P, Chen J, Chada KK, He C, Rosner MR. HMGA2/TET1/HOXA9 signaling pathway regulates breast cancer growth and metastasis. Proc Natl Acad Sci USA. 2013. 110(24):9920-5. PMCID: PMC3683728.

32)   Senyuk V, Zhang Y, Liu Y, Ming M, Premanand K, Zhou L, Chen P, Chen J, Rowley JD, Nucifora G, Qian Z. Critical role of miR-9 in myelopoiesis and EVI1-induced leukemogenesis. Proc Natl Acad Sci USA. 2013. 110(14):5594-9. PMCID: PMC3619279.

33)   Chen P, Price C, Li Z, Li Y, Cao D, Wiley A, He C, Gurbuxani S, Kunjamma RB, Huang H, Jiang X, Arnovitz S, Xu M, Hong G-M, Elkahloun AG, Neilly MB, Wunderlich M, Larson RA, Le Beau MM, Mulloy JC, Liu PP, Rowley JD, Chen J*. miR-9 is an essential oncogenic microRNA specifically overexpressed in mixed lineage leukemia–rearranged leukemia. Proc Natl Acad Sci USA. 2013. 110(28):11511-6. PMCID: PMC3710804.

34)   Huang H, Jiang X, Li Z, Li Y, Song CX, He C, Sun M, Chen P, Gurbuxani S, Wang J, Hong GM, Elkahloun AG, Arnovitz S, Wang J, Szulwach K, Lin L, Street C, Wunderlich M, Dawlaty M, Neilly MB, Jaenisch R, Yang FC, Mulloy JC, Jin P, Liu PP, Rowley JD, Xu M, He C, Chen J*. TET1 plays an essential oncogenic role in MLL-rearranged leukemia. Proc Natl Acad Sci USA. 2013. 110(29):11994-9. PMCID: PMC3718141.

35)   Cheng J, Guo S, Chen S, Mastriano SJ, Liu C, D’Alessio AC, Hysolli E, Guo Y, Yao H, Megyola CM, Li D, Liu J, Pan W, Roden CA, Heydari K, Chen J, Park IH, Ding Y, Zhang Y, and Lu J. An Extensive Network of TET2-Targeting microRNAs Regulates Malignant Hematopoiesis. Cell Reports. 2013. 5(2):471-81. PMCID: PMC3834864.

36)   Velu C, Chaubey A, Phelan J, Horman S, Wunderlich M, Guzman M, Jegga A, Zeleznik-Le N, Chen J, Mulloy J, Cancelas J, Jordan CT, Aronow B, Marcucci G, Bhat B, Gebelein B, Grimes HL. Therapeutic antagonists of microRNAs deplete leukemia-initiating cell activity. J Clin Invest. 2014. 124(1):222-36. PMCID: PMC3871218.

37)   He Y, Jiang X, Chen J*. The role of miR-150 in normal and malignant hematopoiesis. Oncogene. 2014. In press. (Review)

(*serving as the senior/corresponding author)