Henry Heng

Wayne State University | WSU · Center for Molecular Medicine and Genetics

Inhalation exposure to airborne fine particulate matter (aerodynamic diameter < 2.5 µm, PM 2.5 ) is known to cause metabolic dysfunction-associated steatohepatitis (MASH) and the associated metabolic syndrome. Hepatic lipid accumulation and inflammation are the key characteristics of MASH. However, the mechanism by which PM 2.5 exposure induces lip...

If one must prioritize among the vast array of contributing factors to cancer evolution, environmental-stress-mediated chromosome instability (CIN) should easily surpass individual gene mutations. CIN leads to the emergence of genomically unstable life forms, enabling them to grow dominantly within the stable life form of the host. In contrast, sto...

The promises of the cancer genome sequencing project, combined with various -omics technologies, have raised questions about the importance of cancer cytogenetic analyses. It is suggested that DNA sequencing provides high resolution, speed, and automation, potentially replacing cytogenetic testing. We disagree with this reductionist prediction. On...

Cancer cytogenetic analyses often involve cell culture. However, many cytogeneticists overlook interesting phenotypes associated with cultured cells. Given that cytogeneticists need to focus more on phenotypes to comprehend the genotypes, the biological significance of seemingly trivial cellular variations deserves attention. One example is the for...

Karyotype coding, which encompasses the complete chromosome sets and their topological genomic relationships within a given species, encodes system-level information that organizes and preserves genes’ function, and determines the macroevolution of cancer. This new recognition emphasizes the crucial role of karyotype characterization in cancer rese...

Cytogenetic analysis has traditionally focused on the clonal chromosome aberrations, or CCAs, and considered the large number of diverse non-clonal chromosome aberrations, or NCCAs, as insignificant noise. Our decade-long karyotype evolutionary studies have unexpectedly demonstrated otherwise. Not only the baseline of NCCAs is associated with fuzzy...

The dynamic growth of technological capabilities at the cellular and molecular level has led to a rapid increase in the amount of data on the genes and genomes of organisms. In order to store, access, compare, validate, classify, and understand the massive data generated by different researchers, and to promote effective communication among researc...

Organismal evolution displays complex dynamics in phase and scale which seem to trend towards increasing biocomplexity and diversity. For over a century, such amazing dynamics have been cleverly explained by the apparently straightforward mechanism of natural selection: all diversification, including speciation, results from the gradual accumulatio...

The powerful utilities of current DNA sequencing technology question the value of developing clinical cytogenetics any further. By briefly reviewing the historical and current challenges of cytogenetics, the new conceptual and technological platform of the 21st century clinical cytogenetics is presented. Particularly, the genome architecture theory...

We appear to be faced with ‘two truths’ in cancer—one of major advances and successes and another one of remaining short-comings and significant challenges. Despite decades of research and substantial progress in treating cancer, most patients with metastatic cancer still experience great suffering and poor outcomes. Metastatic cancer, for the vast...

The year 2021 marks the 50th anniversary of the National Cancer Act, signed by President Nixon, which declared a national “war on cancer.” Powered by enormous financial support, this past half-century has witnessed remarkable progress in understanding the individual molecular mechanisms of cancer, primarily through the characterization of cancer ge...

In the light of illusions of the Modern Synthesis (MS) listed by Noble (2021a), its key concept, that gradual accumulation of gene mutations within microevolution leads to macroevolution, requires reexamination. In this article, additional illusions of the MS are identified as being caused by the absence of system information and correct history. F...

Gene fusions can give rise to somatic alterations in cancers. Fusion genes have the potential to create chimeric RNAs, which can generate the phenotypic diversity of cancer cells, and could be associated with novel molecular functions related to cancer cell survival and proliferation. The expression of chimeric RNAs in cancer cells might impact div...

The mechanism of biological information flow is of vital importance. However, traditional research surrounding the genetic code that follows the central dogma to a phenotype faces challengers, including missing heritability and two-phased evolution. Here, we propose the karyotype code, which by organizing genes along chromosomes at once preserves s...

Cancer is traditionally labeled a “cellular growth problem.” However, it is fundamentally an issue of macroevolution where new systems emerge from tissue by breaking various constraints. To study this process, we used experimental platforms to “watch evolution in action” by comparing the profiles of karyotypes, transcriptome, and cellular phenotype...

Cancer research has traditionally focused on the characterization of individual molecular mechanisms that can contribute to cancer. Due to the multiple levels of genomic and non-genomic heterogeneity, however, overwhelming molecular mechanisms have been identified, most with low clinical predictability. It is thus necessary to search for new concep...

When discussing chromosomal instability, most of the literature focuses on the characterization of individual molecular mechanisms. These studies search for genomic and environmental causes and consequences of chromosomal instability in cancer, aiming to identify key triggering factors useful to control chromosomal instability and apply this knowle...

The discovery and characterization of abnormal chromosomes have been an important tradition for cytogenetics. In the past 70 years, extensive efforts have been made to illustrate the molecular mechanisms of various chromosomal abnormalities and to apply them for clinical diagnosis and monitoring treatment responses. As a result, clinical cytogeneti...

While the importance of chromosomal/nuclear variations vs. gene mutations in diseases is becoming more appreciated, less is known about its genomic basis. Traditionally, chromosomes are considered the carriers of genes, and genes define bio-inheritance. In recent years, the gene-centric concept has been challenged by the surprising data of various...

While the promise of precision medicine has generated excitement and high expectations, there are challenges for some key assumptions on which the concept is based. Since most common and complex diseases belong to adaptive systems where fuzzy inheritance interacts with the dynamic environment during nonlinear somatic cell evolution, both disease pr...

Micronuclei research has regained its popularity due to the realization that genome chaos, a rapid and massive genome re-organization under stress, represents a major common mechanism for punctuated cancer evolution. The molecular link between micronuclei and chromothripsis (one subtype of genome chaos which has a selection advantage due to the lim...

Health is an adaptive state unique to each person. This subjective state must be distinguished from the objective state of disease. The experience of health and illness (or poor health) can occur both in the absence and presence of objective disease. Given that the subjective experience of health, as well as the finding of objective disease in the...

Chromosomal Coding and Fuzzy Inheritance: The Genomic Basis of Bio-information and Heterogeneity 4.1 SUMMARY Current genomic research, including the observation of a significant degree of genome heterogeneity in normal tissues and cancer samples, has been “full of surprises.” As a result, there has been a strong demand to reexamine genomic concept...

Genome Chaos: Rethinking Genetics, Evolution, and Molecular Medicine transports readers from Mendelian Genetics to 4D-genomics, building a case for genes and genomes as distinct biological entities, and positing that the genome, rather than individual genes, defines system inheritance and represents a clear unit of selection for macro-evolution. In...

Whether sexual reproduction increases biodiversity remains controversial. Traditionally, sex within a species has been thought to increase genetic diversity, inferring an acceleration of macro-evolution, promoting biodiversity. Recently, it was suggested that the main function of sex is to maintain genome integrity, rather than increase genetic div...

Background In the past 15 years, impressive progress has been made to understand the molecular mechanism behind aneuploidy, largely due to the effort of using various -omics approaches to study model systems (e.g. yeast and mouse models) and patient samples, as well as the new realization that chromosome alteration-mediated genome instability plays...

Gulf War illness (GWI) is a chronic multi-symptom disorder impacting one-third of veterans of the 1991 Gulf War. Despite a rapid accumulation of experimental data from various fields, there is no commonly accepted mechanism of this condition. Both the complex etiology and diverse symptoms of GWI have complicated its clinical diagnoses and treatment...

Genome chaos, or karyotype chaos, represents a powerful survival strategy for somatic cells under high levels of stress/selection. Since the genome context, not the gene content, encodes the genomic blueprint of the cell, stress-induced rapid and massive reorganization of genome topology functions as a very important mechanism for genome (karyotype...

Background: The postgenomic era is featured by massive data collection and analyses from various large scale-omics studies. Despite the promising capability of systems biology and bioinformatics to handle large data sets, data interpretation, especially the translation of -omics data into clinical implications, has been challenging. Discussion: In...

The main goals of illustrating the cancer genomic landscape are to identify common gene mutations and profile genetic signatures for specific types or stages of cancer. However, the biggest finding is the overwhelming genetic/nongenetic heterogeneity in cancer, reflected in landscapes of gene mutations, epigenomic changes, genome/karyotype alterati...

High resolution fiber-Fluorescence in situ hybridization (FISH) is an advanced FISH technology that can effectively bridge the resolution gap between probe hybridizing on DNA molecules and chromosomal regions. Since various types of DNA and chromatin fibers can be generated reflecting different degrees of DNA/chromatin packaging status, fiber-FISH...

DNA–protein in situ codetection is a powerful method to study chromosomal/nuclear structure, function, and behavior along with their variations. Following the success of various large-scale genomic projects, the combination of fluorescence immunostaining and FISH may potentially become the method of choice to validate the molecular observations. In...

Background: Gulf War Illness (GWI) impacts 25-30% of gulf war veterans. Due to its heterogeneity in both etiology and symptoms, it has been challenging to establish the commonly accepted case definition for GWI. Equally challenging are the understanding of the general mechanism of GWI and the development of biomarkers useful for its clinical diagn...

Transient and stable vector transfections have played important roles in illustrating the function of specific genes/proteins. The general assumption is that such a platform could effectively link a given gene/protein to gained phenotypes, revealing the mechanism of how a gene works. However, in reality, increased studies have surprisingly noticed...

The importance of human microbiota and their genomes, human microbiome, in health and disease has been increasingly recognized. Human microbiome has tremendous impact in our pathophysiology by modulating metabolic functions, protecting against pathogens, and educating the immune system. In particular, human microbiome is a major player at the inter...

Current cytogenetics has largely focused its efforts on the identification of recurrent karyotypic alterations, also known as clonal chromosomal aberrations (CCAs). The rationale of doing so seems simple: recurrent genetic changes are relevant for diseases or specific physiological conditions, while non clonal chromosome aberrations (NCCAs) are ins...

Big-data-omics have promised the success of precision medicine. However, most common diseases belong to adaptive systems where the precision is all but difficult to achieve. In this commentary, I propose a heterogeneity-mediated cellular adaptive model to search for the general model of diseases, which also illustrates why in most non-infectious no...

With the rapid progress of various large scale sequencing and –omics technologies, molecular cytogenetics is entering a new era: Systems-integrated cytogenetics. Since the genome context rather than gene content defines the genome system by providing system inheritance, the new cytogenetics will play an important role in advancing systems biology....

Influenced by the gene-centric conceptual framework, current genetic studies of disease mainly focus on the characterization of gene mutations or other molecular mechanisms. It is generally accepted that gene mutations are the drivers of diseases. However, it has been very hard to identify these common drivers for most common and complex diseases,...

Contributing reviewers The Editors of Molecular Cytogenetics would like to thank all our reviewers who have contributed to the journal in volume 8 (2015).

Background The unfolded protein response (UPR) refers to intracellular stress signaling pathways that protect cells from the stress caused by accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER). The UPR signaling is crucially involved in the initiation and progression of a variety of human diseases by modulating transcr...

Large-scale genomic projects have unexpectedly challenged the current approach of focusing on genes in disease studies. As common gene mutations are difficult to identify for common/complex diseases, and the diagnostic distinction of gene profile between “normal” and “patient” becomes increasingly blurry, the power of gene-focused studies in medici...

Gulf War illness (GWI) research has generated an abundance of interesting but diverse data. While increased molecular mechanisms have been identified, the high levels of heterogeneity for initial trigger factors, cellular defects, and symptoms continuously challenge the efforts of clinical implications of the research, including the search for biom...

Chromosomal instability ( CIN ) represents a common feature in the majority of cancers. Despite that the search for specific molecular mechanisms linked to the causation or consequences of cancer has become very popular in cancer research, there is no general conceptual framework that unifies the observed diverse molecular findings. By applying the...

Cancer research is at a crossroads. Traditionally, cancer has been thought of as a disease of gene mutation, where the stepwise accumulation of cancer gene mutations is the key, and the identification of common gene mutations has been considered to be essential for diagnosis and treatment. Despite extensive research efforts and accumulated knowledg...

Cancer genome sequencing efforts have resulted in high amounts of diverse, conflicting genomic data, which ultimately challenge the gene mutation theory of cancer. Since each tumor is different, and the genomic landscape of cancer is highly dynamic, a new evolutionary framework and approaches are required to unify the field. While many recent publi...

The basis for the gene mutation theory of cancer that dominates current molecular cancer research consists of: the belief that gene-level aberrations such as mutations are the main cause of cancers, the concept that stepwise gene mutation accumulation drives cancer progression, and the hallmarks of cancer. The research community swiftly embraced th...

Application of traditional somatic evolutionary theory can offer an appropriate context for studying tumor growth at the molecular level. However, high degrees of heterogeneity (especially genome-level heterogeneity) within tumors coupled with a lack of common driver mutations have posed a challenge to the generally accepted stepwise concept of can...

Contributing reviewers The Editors of Molecular Cytogenetics would like to thank all our reviewers who have contributed to the journal in volume 7 (2014).

The high degree of multi-level heterogeneity represents a key challenge for cancer research. Despite its importance, both the theoretical concepts and appropriate tools for proper quantitative analysis are underdeveloped. Specifically, the characterization of heterogeneity in cancer cell populations of different genomic stabilities, and its effect...

The challenge of identifying common expression signatures in cancer is well known, however the reason behind this is largely unclear. Traditionally variation in expression signatures has been attributed to technological problems, however recent evidence suggests that chromosome instability (CIN) and resultant karyotypic heterogeneity may be a large...

Cells are constantly exposed to various internal and external stresses. The importance of cellular stress and its implication to disease conditions have become popular research topics. Many ongoing investigations focus on the sources of stress, their specific molecular mechanisms and interactions, especially regarding their contributions to many co...

Valind et al. report a significant finding, that constitutional aneuploidy itself does not lead to cancer-like chromosomal instability (CIN) (1). This observation, however, may not fully support the conclusion that aneuploidy does not directly lead to chromosomal instability. There is a significant difference between constitutional aneuploidy and t...

Genome chaos, a process of complex, rapid genome re-organization, results in the formation of chaotic genomes, which is followed by the potential to establish stable genomes. It was initially detected through cytogenetic analyses, and recently confirmed by whole-genome sequencing efforts which identified multiple subtypes including “chromothripsis”...

Contributing reviewers The Editors of Molecular Cytogenetics would like to thank all our reviewers who have contributed to the journal in volume 6 (2013).

Genome chaos, a process of complex, rapid genome re-organization, results in the formation of chaotic genomes which is followed by the potential to establish stable genomes. It was initially detected through cytogenetic analyses, and recently confirmed by whole genome sequencing efforts which identified multiple subtypes including "chromothripsis,"...

Abstract Ovarian cancer is the fifth leading cause of death among women worldwide. Characterized by complex etiology and multi-level heterogeneity, its origins are not well understood. Intense research efforts over the last decade have furthered our knowledge by identifying multiple risk factors that are associated with the disease. However, it is...

Multi-level heterogeneity is a fundamental but underappreciated feature of cancer. Most technical and analytical methods used either completely ignore heterogeneity or do not fully account for it, as heterogeneity has been considered as noise that needs to be eliminated. We have used a single-cell and population-based assays to describe an instabil...

Results of various cancer genome sequencing projects have "unexpectedly" challenged the framework of the current somatic gene mutation theory of cancer. The prevalence of diverse genetic heterogeneity observed in cancer questions the strategy of focusing on contributions of individual gene mutations. Much of the genetic heterogeneity in tumors is d...

Whole transcriptome profiling has long been proposed as a method of identifying cancer-specific gene expression profiles. Indeed, a multitude of these studies have generated vast amounts of expression data for many types of cancer, and most have identified specific gene signatures associated with a given cancer. These studies however, often contrad...

Contributing reviewers The Editors of Molecular Cytogenetics would like to thank all our reviewers who have contributed to the journal in volume 6 (2013).

Cell death constitutes a number of heterogeneous processes. Despite the dynamic nature of cell death, studies of cell death have primarily focused on apoptosis, and cell death has often been viewed as static events occurring in linear pathways. In this article we review cell death heterogeneity with specific focus on 4 aspects of cell death: the ty...

In a departure from traditional gene-centric thinking with regard to cytogenetics and cytogenomics, the recently introduced genome theory calls upon a re-focusing of our attention on karyotype analyses of disease conditions. Karyotype heterogeneity has been demonstrated to be directly involved in the somatic cell evolution process which is the basi...

The archetype driving the drug targeting approach to cancer therapy is the success of imatinib against chronic phase chronic myeloid leukemia (CML-CP). Molecular targeting success of this magnitude has yet to be repeated for most solid tumors. To answer why imatinib remains an exception of cancer research, we summarize key features and patterns of...

The chromosome has long been viewed as a structure that ensures faithful segregation of the genetic materials to daughter cells. However, it is now apparent that the chromosome plays a central role in defining the genetic network through the genome context. One often-confused phenomenon bridging studies of interphase chromatin and mitotic chromosom...

Assisted reproductive technologies have been used to achieve pregnancies since the first successful test tube baby was born in 1978. Infertile couples are at an increased risk for multiple miscarriages and the application of current protocols are associated with high first-trimester miscarriage rates. Among the contributing factors of these higher...

Based on the popular reductionist tradition, the advancement of molecular medicine has generated a great deal of promise. In reality, however, much of the promise will not be realized due to high levels of system complexity. The conventional wisdom is that, if we try harder, and dissect the system further by pushing new technologies, we should be a...

Endoplasmic Reticulum (ER) stress refers to a condition of accumulation of unfolded or misfolded proteins in the ER lumen. A variety of biochemical stimuli or pathophysiologic conditions can directly or indirectly induce ER stress, leading to activation of an ER-originated adaptive signaling response called Unfolded Protein Response (UPR). Recent s...

Cell death constitutes a number of heterogeneous processes. Despite the dynamic nature of cell death, studies of cell death have primarily focused on apoptosis, and cell death has often been viewed as static events occurring in linear pathways. In this article we review cell death heterogeneity with specific focus on 4 aspects of cell death: the ty...

The recently introduced genome theory of cancer evolution provides a new framework for evolutionary studies on cancer. In particular, the established relationship between the large number of individual molecular mechanisms and the general evolutionary mechanism of cancer calls upon a change in our strategies that have been based on the characteriza...

Cancer is commonly viewed as a disease of the stepwise accumulation of gene mutations. However, genetic and epigenetic heterogeneity (GEH) is pervasive in cancer, playing a key role in promoting cancer progression. GEH occurs at three primary levels, the genome, gene and epigenetic levels and increases during the aging process and during stress. GE...

Secondary malignancies (SMs) in Hodgkin lymphoma (HL) are thought to be related to exposure to alkalating agents, topoisomerase II inhibitors and ionizing radiation, and tend to occur a decade after initial therapy. We report a 14 year old autistic male, who developed malignant fibrous histiocytoma (MFH) two years after autologous stem cell transpl...

Chromosome fragmentation (C-Frag) is a newly identified MCD (mitotic cell death), distinct from apoptosis and MC (mitotic catastrophe). As different molecular mechanisms can induce C-Frag, we hypothesize that the general mechanism of its induction is a system response to cellular stress. A clear link between C-Frag and diverse system stresses gener...

While our understanding of gene-based biology has greatly improved, it is clear that the function of the genome and most diseases cannot be fully explained by genes and other regulatory elements. Genes and the genome represent distinct levels of genetic organization with their own coding systems; Genes code parts like protein and RNA, but the genom...

The spectral karyotyping procedure of in situ hybridization with chromosome-specific probes assigns a unique colour code to each of the 21 mouse mitotic chromosomes. We have adapted this procedure to meiotic prophase chromosomes, and the results show that each of the pachytene or metaphase I bivalents can be identified. This technique has the poten...

A single expressing copy of the human protamine domain was randomly inserted into an intron of Cyp2c38. The transgenic locus was shown to recapitulate the level of expression observed in normal human testis while not perturbing endogenous protamine expression. The development of an interspecies tiling array was pursued to enable direct comparison o...

A recent Viewpoint article (Eichler, E. E. et al. Missing heritability and strategies for finding the underlying causes of complex disease. Nature Rev.

For over a century, the paradigm has been that sex invariably increases genetic variation, despite many renowned biologists asserting that sex decreases most genetic variation. Sex is usually perceived as the source of additive genetic variance that drives eukaryotic evolution vis-à-vis adaptation and Fisher's fundamental theorem. However, evidence...

Based on the gene and pathway centric concept of cancer, current approaches to cancer drug treatment have been focused on key molecular targets specific and essential for cancer progression and drug resistance. This approach appears promising in many experimental models but unfortunately has not worked well in the vast majority of cancers in clinic...

Mitotic cell death is an important form of cell death, particularly in cancer. Chromosome fragmentation is a major form of mitotic cell death which is identifiable during common cytogenetic analysis by its unique phenotype of progressively degraded chromosomes. This morphology however, can appear similar to the morphology of premature chromosome co...