Hong-Qiang Heng
Office Address
3226 Scott Hall
540 E. Canfield
Detroit, MI 48201
Position Title
ProfessorBiography
Dr. Henry H.Q. Heng is an Associate Professor in the Center of Molecular Medicine and Genetics and Department of Pathology at the Wayne State University School of Medicine. He received his PhD in Medical Genetics under Dr. Lap-Chee Tsui at the Hospital for Sick Children (Toronto), and completed his post-doc training in chromosomal studies under Dr. Peter Moens at York University. He joined Wayne State in 1999.
Dr. Hengs current research focuses on developing the genome theory of cancer and organismal evolution. He has co-authored over 165 peer reviewed publications with total citations of over 9,800. He serves on the editorial board of six international journals, including serving as the co-editor-in-chief of Molecular Cytogenetics.
Education Training
Ph.D., Toronto, 1994.
Medical Education Responsibilities
Undergraduate student lecture responsibilities
2007-2009 Guest lecture: Cancer Biology, Biology Department, School of Liberal Arts and Science.
Graduate student lecture responsibilities
1999-2011 Wayne State University School of Medicine.
Shared Responsibility: Advanced Human Genetics (7060)
2008 Guest lecture: Cancer Prevention, KCI, School of Medicine
2009-2010 Shared Responsibility: Cancer Biology
2011 Guest lecture: Molecular Evolution, Biology Department
2013 Shared Responsibility, Stem Cell Biology Course (PSL 7700)
Mentorships (over the past 3 years)
GRADUATE AND UNDERGRADUATE TRAINING
Rotation graduate student KM (2009)
Rotation graduate student BA (2010)
Undergraduate research training student MT (2009-2010)
Summer Undergraduate Research Program student SR (2010)
Ph.D student BA (2010-present)
Rotation graduate student NG (2010)
Rotation graduate student SH (2010-2011)
Rotation graduate student CS (2011)
Rotation graduate student RM (2011)
Rotation graduate student CG (2012)
POST-DOCTORAL AND OTHER TRAINING
Special Training (visiting Scientist) Dr. SL (2000-2001)
Medical resident research training Dr. GG (2007)
Medical resident research training Dr. AC (2008)
Post-Dr training CY (2004-2008)
Post-Dr training Dr. JS (2009-present)
Mentor for medical resident training grant Dr. JK (2011)
Areas of Interest
Molecular cytogenetics; genome structure and function; genomic instability and cancer progression.
Research
Key contributions over the past three years
In the past 3 years, our group has made a number of fundamental contributions to both cancer biology and evolutionary studies.
In 2010, we published the evolutionary mechanism of cancer, which recommends a dramatic paradigm shift in cancer research. Our group has been advocating this shift for years. Despite the fact that we have been invited to participate in many NCI think tank meetings and various high level discussions, getting others to move in this new direction has been extremely challenging. Recently however, the situation has been dramatically changing. The accumulated data from the cancer genome sequencing efforts has validated all of our predictions based on the genome theory of non-clonal cancer evolution. Significantly, our original discoveries of punctuated cancer evolution and genome chaos have been confirmed by deep sequencing from a large number of recent publications in Cell and Nature. Our concepts were referred to as the HengDuesberg causality by a recent book chapter in Advanced Cancer Research where our concepts were extensively discussed. In addition, a recent review article titled Evolution of the cancer genome by a well-known leader in evolutionary modeling has highlighted our discoveries (Trends in Genetics, 2012). Similarly, other papers have praised our genome theory of cancer evolution (PLoS Genetics, 2012).
In 2011, we published a milestone article in Evolution (featured on the cover) that systematically re-evaluates the main function of sex, a key evolutionary question for over a century. Our analysis redefines the function of sex and has generated a shockwave within the field. Also, recently, our theory has gained strong support from computational modeling (PLoS
Computational Biology, 2012). They demonstrated that a faster evolutionary rate decreases the abundance of newly formed species and thus decreases long-term biodiversity. This study represents a new wave of research validating our concept that the key to species continuity is short term gene mediated dynamics and long term stasis conserved by genome constraint.
In the past three years, Wayne State University has issued a number of separate press releases reporting achievements from my group. These releases have generated high levels of national and international interest that has impressed the leadership of our University. Publicity from our achievements has resulted in hundreds of news sources reporting our stories in multiple languages, and we have been interviewed by Newspapers, bloggers from different countries including Science Daily News, Beijing News, Agoravox (France) and Discovery Magazine. Our contributions have been included in various Encyclopedias. Our group has also been invited to write a chapter on cancer genetic/epigenetic heterogeneity for several journals including Encyclopedia of Life Sciences, and editing a special issue for two journals including Cancer and Metastasis Reviews (Journal Impact Factor: 10.573).
In 2012, our group completed three major projects titled: the molecular characterization of genome chaos; single cell mediated heterogeneity and the genome defines the network structure. These three papers will likely generate high levels of interest in the field (manuscripts are now ready for submission). In addition, we have linked elevated genome alterations to Chronic Fatigue Syndrome (CFS) patients based on 15 patients and 20 controls. We anticipate that this report will be well received by the medical community (manuscript in preparation), as in spite of decades of research on this illness, there is still no reliable diagnostic genetic marker for CFS. We believe that genome instability will serve as a clinical marker for CFS.
Research Interests
Since joining Wayne State University in 1999, Dr Heng's group has been working on the new genome theory and applying its principles to the study of common and complex diseases/illnesses, induction of cancer and recently GWI and CFS. This approach is a departure from the gene centric concept that focuses on identifying specific genes responsible for complex disease and illness, and his theory focuses on genome system instability. According to the genome theory, a large number of genetic and environmental factors can serve as initiating stress which leads to genome instability and triggers diverse symptoms mediated by stochastic genomic changes. Genome alterations serve as a means for adaptation, but also lead to disease and illness conditions.
Publications
Abdallah BY, Horne SD, Stevens JB, Liu G, Ying AY, Vanderhyden B, Krawetz SK, Gorelick R, Heng HH (2013). Single cell heterogeneity: why unstable genomes are incompatible with average profiles. Cell Cycle 12(23). (in press).
Stevens JB, Liu G, Abdallah BY, Horne SD, Ye KJ, Bremer SW, Ye CJ, Krawetz SA, Heng HH. (2013) Unstable genomes elevate transcriptome dynamics. International Journal of Cancer (in press).
Stevens JB, Horne SD, Liu Guo, Abdallah Batoul, Ye CJ., Heng HH. (2013) Chromosomal instability and transcriptome dynamics in cancer. Cancer and Metastasis Review (Epub ahead of print).
Heng HH, Bremer SW, Stevens JB, Horne SD, Liu Guo, Abdallah Batoul, Ye KJ, Ye CJ. (2013) Chromosomal Instability (CIN): what it is and why it is crucial to cancer evolution. Cancer and Metastasis Reviews (epublication, online).
Stevens J.B. • Abdallah B.Y. • Liu G. • Horne S.D. • Bremer S.W. • Ye K.J. • Huang J.Y. • Kurkinen M. • Ye C.J. • Heng H.H. (2013) Heterogeneity of Cell Death Cytogenet Genome Res. 139:164-173.
Heng H.H. • Liu G. • Stevens J.B. • Abdallah B.Y. • Horne S.D. • Ye K.J. • Bremer S.W. • Chowdhury S.K. • Ye C.J. (2013) Karyotype Heterogeneity and Unclassified Chromosomal Abnormalities. Cytogenet Genome Res. 139:144-57.
Horne SD, Stevens JB, Abdallah BY, Liu G, Bremer SW, Ye CJ, Heng HH. (2013) Why imatinib remains an exception of cancer research. J Cell Physiol. 228(4):665-70.
Stevens, Joshua B, Abdallah, Batoul Y, Horne, Steven D, Liu, Guo, Bremer, Steven W, and Heng, Henry H (2011) Genetic and Epigenetic Heterogeneity in Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net.
Heng HH, Liu G, Stevens JB, Bremer SW, Ye KJ, Abdallah BY, Horne SD, Ye CJ. (2011) Decoding the genome beyond sequencing: The new phase of genomic research. Genomics. 98:242-52.
Stevens JB, Abdullah BY, Liu G, Ye CJ, Horne SD, Wang G, Savasan S, Shekhar M, Krawetz SA, Huttemann M, Tainsky MA, Wu GS, Xie Y, Zhang K, Heng HH. (2011) Diverse system stresses: common mechanisms of chromosome fragmentation. Cell Death Dis. 2:e178.
Heng HH. (2013) Chapter 12: Bio-complexity challenging reductionism. In Handbook on system and complexity in health. pp 193-208. Sturmberg and Martin (eds). Springer.
Heng HH. (2013). Genomics: HeLa genome versus donor's genome. Nature 501, 167.
Heng, HH, Stevens, JB, Bremer, SW, et al. (2011) Evolutionary mechanisms and diversity in cancer. Advances in Cancer Research - Intratumor diversity and clonal evolution in cancer 112:217-53.
Heng HH, Liu G, Stevens JB, Bremer SW, Ye KJ, Ye CJ. (2010)b. Genetic and epigenetic heterogeneity in cancer: the ultimate challenge for drug theory. Current Drug Target 11:1304-1316.
Heng HH, Stevens JB, Bremer SW, Ye KJ, Liu G, Ye CJ. (2010)a. The evolutionary mechanism of cancer. J Cellular Biochemistry 109: 1072-1084.
Heng HH. (2010) Missing heritability and stochastic genome alterations. Nat Rev Genet. 11:813.
Heng HH. (2009). The genome-centric concept: resynthesis of evolutionary theory. BioEssays. 31: 512-25.
Heng HH, Bremer, S, Stevens, J, Ye, K, Liu, G and Ye CJ. (2009). Genetic and epigenetic heterogeneity in cancer: a genome-centric perspective. Journal of Cellualr Physiology. 220: 538-547.
Ye CJ, Stevens JB, Liu G, Bremer SW, Jaiswal AS, Ye KJ, Lin MF, Lawrenson L, Lancaster WD, Kurkinen M, Liao JD, Gairola CG, Shekhar MP, Narayan S, Miller FR, Heng HH. (2009). Genome based cell population heterogeneity promotes tumorigenicity: the evolutionary mechanism of cancer. J Cell Physiol. 219:288-300.
Ye CJ , Lawrenson L, Liu G, Stevens JB, Ye KJ, Bremer SW, and Heng HH, (2009). Chapter 19: Simultaneous fluorescence immunostaining and FISH. In Liehr T edited: Fluorescence in situ hybridization (FISH) – Application. Springer Publisher. Pp193-216.
Espino PS, Pritchard S, Heng HH, Davie JR. (2009). Induction of H3 phosphorylation at Serine 10 by the Ras-MARK pathway correlates with nonclonal chromosomal aberrations in pancreatic cancer cells. Int J Cancer 124(3):562-7.
Heng HH . (2008). The conflict between complex systems and reductionism. JAMA. 300: 1580-1581.
Whittington PJ, Piechocki MP, Heng HH, Jacob JB, Jones RF, Back JB and Wei WZ. (2008). DNA vaccination controls Her-2+ tumors that are refractory to targeted therapies. Cancer Res. 68: 7502-7511.
Heng HH, Stevens J, Lawrenson L, Liu G, Ye KJ, Bremer, S and Ye, CJ. (2008). Patterns of genome dynamics and cancer evolution. Cellular Oncology 30:513-4.
Gong L, Yao F, Hockman K, Heng HH, Morton GJ, Takeda K, Akira S, Low MJ, Rubinstein M, Mackenzie RG. (2008). Stat3 is required in hypothalamic Agrp/Npy neurons for normal energy homeostasis. Endocrinology. 149:3346-54
Heng HH (2008). The gene-centric concept: a new liability? BioEssays 30: 196-187.
Heng HH (2007). Challenging reproduction assumptions. SCIENTIST 21: 16-16.
Heng HH (2007). Elimination of altered karyotypes by sexual reproduction preserves species identity. Genome 50: 517-524.
Tait LR, Pauley RJ, Santner SJ, Heppner GH, Heng HH, Rak JW, Miller FR.(2007). Dynamic stromal-epithelial interactions during progression of MCF10DCIS.com xenografts. Int J Cancer. 120: 2127-2134.
Heng HH (2007). Cancer genome sequencing: the challenges ahead. BioEssays 29: 783-794.
Stevens JB, Liu G, Bremer SW, Ye KJ, Xu W, Sun Y, Wu GS, Savasan S, Krawetz SA, Ye CJ and Heng HH. (2007). Mitotic cell death by chromosome fragmentation. Cancer Research 67: 7686-7694.
Beatty, B., and Heng, HH. (2007). Gene mapping by Fluorescence in situ hybridization. In Meyer R ed Genomics and Genetics: From molecular details to analysis and techniques. Vol 2 p713-748. Wiley-VCH.
Ye CJ, Liu G, Bremer SW, Heng HH. (2007). Invited review: Cancer Genomics: The dynamics of cancer chromosomes and genomes. Cytogenetics and Genome Research: Cancer Genomics 118:237-246.
Heng HH , Stevens JB, Liu G, Bremer SW, Ye KJ, Reddy PV, Wu GS, Wang YA, Tainsky MA, Ye CJ. (2006) Stochastic cancer progression driven by non-clonal chromosome aberrations. Journal of Cellular Physiology 208: 461-472.
Heng HH , Bremer SW, Stevens J, Ye KJ, Miller F, Liu G, Ye CJ. (2006). Prospect: Cancer progression by non-clonal chromosome aberrations. J Cell Biochem. 98: 1424-1435 (featured by cover).
Heng HH., Liu, G., Bremer, S. Ye, K.J., Stevens J., and Ye C.J. (2006). Clonal and non-cloal chromosome aberrations and genome variation and aberration. Genome 49: 195-204 (featured by cover).
Woodward KJ, Cundall M, Sperle K, Sistermans EA, Ross M, Howell G, Gribble SM, Burford DC, Carter NP, Hobson DL, Garbern JY, Kamholz J, Heng H , Hodes ME, Malcolm S, Hobson GM. (2005). Heterogeneous duplications in patients with Pelizaeus-Merzbacher disease suggest a mechanism of coupled homologous and nonhomologous recombination. Am J Hum Genet . 77:966-87.
Roberts PC, Mottillo EP, Baxa AC, Heng HH , Doyon-Reale N, Gregoire L, Lancaster WD, Rabah R, Schmelz EM. (2005). Sequential molecular and cellular events during neoplastic progression: a mouse syngeneic ovarian cancer model. Neoplasia 7:944-956.
Shen, K.C., Heng, H., Wang, Y., Lu, S., Liu, G., Deng, C.H., Brooks , S.C. , and Wang, Y.A. (2005). ATM and p21 cooperate to suppress aneuploidy and subsequent tumor development. Cancer research 65: 8747-8753.
Biliran H., Wang, Y., Banerjee, S., Xu, H, Heng, H., Thakur, A., Bolling, A., Sarkar, FH and Liao JD (2005). Overexpression of cyclin D1 promotors tumor cell growth and confers resistance to Cisplatin-mediated apoptosis in an elastase-myc transgene expression pancreatic tumor cell line. Clinical Cancer Research 11; 1075-6086 (cover and featured article).
Wu, XH., Avni, D., Li ,X., Zhao, Q., Lin,Y., Heng, H., and Livingston, D. (2004). SV40 T antigen interacts with Nbs1 to disrupt cellular replication control. Genes & Development 18: 1305-1316.
Derjuga A, Gourley TS, Holm TM, Heng HH , Shivdasani RA, Ahmed R, Andrews NC, Blank V . (2004). Complexity of CNC Transcription Factors as Revealed by Gene Targeting of the Nrf3 Locus. MCB 24: 3286-3294.
Heng, H H ., Goetze, S., Ye, C.J., Liu, G., Stevens, J.B., Bremer, S.W., Bode, J., Wykes, SM., and Krawetz, SA. (2004). Chromatin loops are selectively anchored using Scaffold/matrix attachment regions. J Cell Sci . 117: 999-1008 (featured article).
Heng, H.H.Q ., Stevens, J., Liu, G., Bremer, S.B. and Ye C.J. (2004). Imaging genome abnormalities in cancer research (invited review). Cell & Chromosomes 3:1
Beatty, B., and Heng, H.H. (2004). Gene mapping by Fluorescence in situ hybridization. In Meyer R ed Encyclopedia of Molecular Cell Biology and Molecular Medicine. Vol 5 p137-171. Wiley-VCH
Kolas, N.K., Yuan, L., Hoog, C., Heng, H.H.Q., Marcon, E.,, and Moens, P.B. (2003). Meiotic chromosome cores deficient in structural proteins SCP3 and SCP2 are capable of chromatin loop attachment with possible impaired specificity. Cytogent Genome Res (in press).
Heng, H.H.Q., Ye, C.J., Yang, FT., Ebrahim, S., Liu, G., Bremer, S., Thomas, MC., Ye. J., Chen, T.J., Tuck-Muller, C., Yu, J.W., Krawetz, SA., and Johnson, A (2003). Analysis of marker or complex chromosomal rearrangements present in pre-and postnatal karyotypes utilizing a combination of G-banding, SKY and FISH. Clinical Genetics 63: 358-367.
Bode, J., Goetze, S., Heng, HH., Krawetz, SA, and Benham, C. (2003). From DNA structure to gene expression: Mediators of nuclear compartmentalization and dynamics. Chromosome Res 11: 435-445.
Scherer S, Heng HH, et al, (2003). Human Chromosome 7: DNA Sequence and Biology. Science 300: 767-772.
Yang, LV., Heng, H.H., Wan, J.,, Southwood,C.M., Gow, A and Li, L. (2003) Alternate promoters and polyadenylation regulate tissue-specific expression of Hemogen isoforms during hematopoisis and spermatogenesis. Developmental Dynamics. 228: 606-616.
Takeuchi, T., Heng, H.H.Q., Ye, C. J., Liang, S.B., Sonobe, H and Yuji Ohtsuki, Y. (2003). Down-regulation of a novel actin-binding molecule, skeletrophin, in malignant melanoma. Am J Pathology 163: 1395-1404.
Cheung, J., Wilson, MD., Zhang, J., Khaja R., MacDonal, JR., Heng, H.H.Q., Koop, B.F., and Scherer, SW. (2003). Recent segmental and gene duplications in the mouse genome. Genome Biology 4: R47.
Heng, H.H.Q (2002). High resolution FISH mapping using chromatin and DNA fiber. In: Beatty et al ed, FISH: A Practical Approach. p.77-92. Oxford University Press.
Shekhar, M.P.V., Lyakhovich, A., Visscher, D. W., Heng, H., and Kondrat, N. (2002). Rad 6 overexpression induces multinucleation, centrosome amplification, abnormal mitotic, aneuploidy, and transformation. Cancer Research 62: 2115-2124.
Dong, S., Leung, KKH., Pelling, A.L., Lee, PYT., Tang, A., Heng, HHQ., Tsui, L-C., Tease, C., Fisher, G., Stell, K.P., and Cheah, KSE (2002). Circling, deafness and yellow coat colour displayed by the chromosome 3 mouse mutant yellow submarine (Ysb) and light coat circling (Lcc). Genomics 79(6):777-84.
Schmid, C., Heng, H.H.Q., Rubin, C., Ye, C.J., and Krawetz, SA (2001). Sperm nuclear matrix of the PRM1-PRM2-TNP2 domain is independent of ALU methylation. Hum Mole Reproduction 7: 903-911.
Heng, H.H.Q., Krawetz, SK., Lu, W., Bremer, S., Liu, G., and Ye, C.J. (2001). Re-defining the chromatin loop domain. Cytogent Cell Genet 93: 155-161.
Ye, J., Lu, W., Moens, P., Liu, G., Bremer, S., Wang Y, Hughes, M., Krawetz, S., and Heng, H.H.Q. (2001). The combination of SKY and specific loci detection with FISH or Immunostaining. Cytogenetics and Cell Genetics 93: 195-202.
Heng, H.H.Q., Liu, G., Lu, W., Bremer, S., Ye C.J., Hughes, M., and Moens, P. (2001). Multicolor SKY painting of mouse meiotic chromosomes. Genome 44: 293-298.
Ding, B.C., Witt, T.L., Hukku, B., Heng, H., Zhang, L., and Matherly, L.H. (2001). Deletions and translocations of the reduced folate carrier gene are associate with profound loss of gene expression in methotrexate resistant K562 human erythroleukemia cells. Biochem. Pharmacol 61: 665-675.
Liu, G., Lu, W., Bremer, S., Hameister, H., Schreiner, B., Hughes, M., and Heng, H.H.Q. (2000). Spectral Karyotyping of Mouse Cell Line WMP2. Cytogenet Cell Genet 90: 271-274.
Lee DK, Lynch KR, Nguyen T, Im D, Cheng R, Saldivia VR, Liu Y, Liu IS, Heng H.H.Q, Seeman P, George SR, O'Dowd BF, Marchese A. (2000). Cloning and characterization of additional members of the G protein-coupled receptor family. Biochim Biophys Acta 1490(3):311-323.
Heng, H.H.Q, Spyropoulos, B., Moens, PB (2000). DNA-protein in situ co-detection. Methods in Molecular Biology: In situ hybridization protocols. Vol: 123: 15-27. Clifton, New Jersey, Humana Press.
Heng, H.H.Q (2000). Released chromatin or DNA fiber preparation for high-resolution fiber FISH. Methods in Molecular Biology: In situ hybridization protocols. Vol: 123: 69-81. Clifton, New Jersey, Humana Press.