Henry H.Q. Heng, PhD

Education

University of Toronto, PhD, 1994

Research Focus

Our group is searching for a new genome information-based framework of genomics, evolution and, their clinical implications.  On a theoretical level, we have introduced the Genome Architecture Theory, which makes two key distinctions: 1. Genomic topology, or the order of genes and genetic elements on chromosomes and within the 3D-genome, is a new layer of key genomic information. and 2. “System inheritance”, the inheritance of genome topology, rather than gene/epi-gene defined “parts inheritance”, represents the blueprint of bio-systems.

We are also investigating karyotype coding, a chromosome-level code that organizes gene interactive networks. This means that the phenotype of an organism can drastically change solely due to a change in the karyotype coding. Thus, the neo-Darwinian mechanism of natural selection needs to be drastically changed as macroevolution does not equate to microevolution + time. More recently, we have been exploring the relationship between evolution and genomic/non-genomic information flow (creation, preservation, modification, and usage)

From our experimental work, we have discovered a “two-phased" model of cancer evolution (punctuated macro-cellular evolution and stepwise Darwinian micro-cellular evolution) that has been commonly detected during the entire process of cancer formation (including immortalization, transformation, metastasis to drug resistance).  Within the punctuated phase, genome chaos dominates, which explains the rapid cancer evolution which cannot be explained by the evolution of individual cancer genes. Upon the formation of the survivable cancer genomes, the microevolutionary phase is soon followed promoted by stochastic cancer genome mutations and/or epigenetic dynamics. We have also established the concept/methodology of measuring genome instability based on the frequency of non-clonal chromosome aberrations, which is essential to understand the diverse molecular mechanisms of cancer in the context of somatic cell evolution.

Mentoring

Not accepting new M.S. students in 2024/2025

Not accepting new Ph.D. students in 2024/2025

Recent Publications

Books:

 

Heng HH. Genome Chaos: Rethinking Genetics, Evolution, and Molecular Medicine. Academic Press, Total page 548 (June 1 2019) (2020 PROSE award finalist - the Association of American Publishers Awards for Professional and Scholarly Excellence).                           

 Heng HH. Debating Cancer: The Paradox in Cancer Research.  World Scientific Publish 2015. Total page 464.

Heng HH. (Editor) 2013. Genetic Heterogeneity and Human Diseases. Karger Publisher

 

Original Observations/Review Articles/Book Chapters:

Heng J, Heng HH. Karyotype coding: Karyotype coding: The creation and maintenance of system information for complexity and biodiversity.  [published online ahead of print, 2021 Jul 5]. Biosystems. 2021;208:104476. doi:10.1016/j.biosystems.2021.104476

Ye JC, Horne S, Zhang JZ, Jackson L, Heng HH. Therapy Induced Genome Chaos: A Novel Mechanism of Rapid Cancer Drug Resistance. Front Cell Dev Biol. 2021;9:676344. Published 2021 Jun 10. doi:10.3389/fcell.2021.676344

Heng J, Heng HH. Two-phased evolution: Genome chaos-mediated information creation and maintenance. [published online ahead of print, 2021 May 13]. Prog Biophys Mol Biol. 2021;S0079-6107(21)00033-X. doi:10.1016/j.pbiomolbio.2021.04.003

Heng J, Heng HH. Genome chaos: Creating new genomic information essential for cancer macroevolution. [published online ahead of print, 2020 Nov 13]. Semin Cancer Biol. 2020;S1044-579X(20)30224-8. doi:10.1016/j.semcancer.2020.11.003

Ye CJ, Sharpe Z, Heng HH. Origins and Consequences of Chromosomal Instability: From Cellular Adaptation to Genome Chaos-Mediated System Survival.  Genes (Basel). 2020;11(10):1162. Published 2020 Sep 30. doi:10.3390/genes11101162

Ye CJ, Chen J, Liu G, Heng HH. Somatic Genomic Mosaicism in Multiple Myeloma. Front Genet. 2020;11:388. Published 2020 Apr 22. doi:10.3389/fgene.2020.00388

Ye CJ, Stilgenbauer L, Moy A, Liu G, Heng HH. What Is Karyotype Coding and Why Is Genomic Topology Important for Cancer and Evolution? Front Genet, 2019, 10:1082. doi: 10.3389/fgene.2019.01082.

Ye CJ, Sharpe Z*, Alemara S, Mackenzie S, Liu G, Abdallah B, Horne S, Regan S, Heng HH. Micronuclei and Genome Chaos: Changing the System Inheritance. Genes (Basel), 2019, 10(5). pii: E366. doi: 10.3390/genes10050366.

Sturmberg JP, Picard M, Aron DC, Bennett JM, Bircher J, deHaven MJ, Gijzel SMW, Heng HH, Marcum JA, Martin CM, Miles A, Peterson CL, Rohleder N, Walker C, Olde Rikkert MGM, Melis RJF. Health and Disease-Emergent States Resulting From Adaptive Social and Biological Network Interactions. Front Med (Lausanne). 2019, 6:59. doi: 10.3389/fmed.2019.00059.

Heng HH, Liu G, Alemara S, Regan S, Zachary A, Ye CJ (2019). The Mechanisms of how genomic heterogeneity impacts bioemergent properties: The challenges for precision medicine. In: Sturmberg JP (ed.), Embracing Complexity in Health. Springer Nature Switzerland AG, Pp 95-109.

Ye CJ, Liu G, Heng HH. (2018) Experimental Induction of Genome Chaos. In: Pellestor F. (eds) Chromothripsis. Methods in Molecular Biology, vol 1769. Humana Press, New York, NY. Pp 337-352. doi: 10.1007/978-1-4939-7780-2_21.

JY Christine, S Regan, G Liu, S Alemara, HH Heng. Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems. Molecular cytogenetics 2018, 11 (1), 31.

Heng HH, Liu G, Regan S and Ye CJ. (2018). Linking Gulf War Illness to genome instability, somatic evolution, and complex adaptive systems. In: Putting systems and complexity sciences into practice. J.P. Sturmberg (ed). Springer International Publishing. Pp65-77.

Heng HH. The Genomic Landscape of Cancers (Chapter 5) (2017). In: Ecology and Evolution of Cancer, edited by Beata Ujvari, Benjamin Roche, Frederic Thomas,  Elseiver. pp. 69-83.

Stepanenko A, Heng HH.  Transient and stable vector transfection: Pitfalls, off-target effects, artifacts. Mut Research 2017, 773: 91-103.

Ye CJ, Heng HH. (2017). High Resolution Fiber-Fluorescence In Situ hybridization. Methods Mol Biol, 1541, 151-166.

Ye CJ, Liu G, Heng HH (2016). Simultaneous Fluorescence Immunostaining and FISH.  Fluorescence In Situ Hybridization (FISH), 2016. Ed Liehr, Springer, pp 301-325.

Heng HH, Horne SD, Stevens SB, Abdallah BY, Liu G, Ye KJ, Chowdhury SK, Bremer SW, Zhang K and Ye CJ. (2016).  Heterogeneity mediated system complexity: the ultimate challenge for studying common and complex diseases.  In: The Value of Systems and Complexity Sciences for Healthcare, ed. Sturmberg JP (Springer International Publishing), pp. 107-120.

Horne SD, Wexler M, Stevens JB, Heng HH. Insights on processes of evolutionary tumor growth. Atlas Genet Oncol Haematol, “Deep Insight session”  March 2015. 

Horne SD, Ye CJ, . Chromosomal instability (CIN) in cancer. eLS, 2015, 1-9. 

Horne SD, Pollick SA, Heng HH. Evolutionary mechanism unifies the hallmarks of cancer. Int J Cancer. 2015 136:2012-21. doi: 10.1002/ijc.29031. PMID: 24957955

Horne SD, Chowdhury SK, Heng HH. Stress, genomic adaptation, and the evolutionary trade-off. Front Genet. 2014 5:92. doi: 10.3389/fgene.2014.00092. eCollection 2014. PMID:24795754

Heng HH. Distinguishing constitutional and acquired nonclonal aneuploidy. Proc Natl Acad Sci U S A. 2014 111(11):E972. doi: 10.1073/pnas.1323636111. Epub 2014 Jan 31. PMID: 24488973

Liu G, Stevens JB, Horne SD, Abdallah BY, Ye KJ, Bremer SW, Ye CJ, Chen DJ, Heng HH.  Genome chaos: survival strategy during crisis. Cell Cycle. 2014;13(4):528-37. doi: 10.4161/cc.27378.  PMID:24299711

Stevens JB, Liu G, Abdallah BY, Horne SD, Ye KJ, Bremer SW, Ye CJ, Krawetz SA, Heng HH.Unstable genomes elevate transcriptome dynamics. Int J Cancer. 2014 134(9):2074-87.  PMID: 24122714

Abdallah BY, Horne SD, Stevens JB, Liu G, Ying AY, Vanderhyden B, Krawetz SA, Gorelick R, Heng HH. Single cell heterogeneity: why unstable genomes are incompatible with average profiles. Cell Cycle. 2013 Dec 1;12(23):3640-9. doi: 10.4161/cc.26580.  PMID: 24091732

Heng HH. Genomics: HeLa genome versus donor's genome. Nature. 2013 501(7466):167. doi: 10.1038/501167d. PMID: 24025829

Heng HH, Bremer SW, Stevens JB, Horne SD, Liu G, Abdallah BY, Ye KJ, Ye CJ. Chromosomal instability (CIN): what it is and why it is crucial to cancer evolution. Cancer Metastasis Rev. 2013 32(3-4):325-40. doi: 10.1007/s10555-013-9427-7. PMID: 23605440