John B. Hogenesch
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John B. Hogenesch (born May 29, 1967) is an American
chronobiologist Chronobiology is a field of biology that examines timing processes, including periodic (cyclic) phenomena in living organisms, such as their adaptation to solar- and lunar-related rhythms. These cycles are known as biological rhythms. Chronobi ...
and Professor of
Pediatrics Pediatrics ( also spelled ''paediatrics'' or ''pædiatrics'') is the branch of medicine that involves the medical care of infants, children, adolescents, and young adults. In the United Kingdom, paediatrics covers many of their youth until th ...
at the Cincinnati Children's Hospital Medical Center. The primary focus of his work has been studying the network of mammalian clock genes from the genomic and computational perspective to further the understanding of circadian behavior. He is currently the Deputy Director of the Center for Chronobiology, an Ohio Eminent Scholar, and Professor of Pediatrics in the Divisions of Perinatal Biology and Immunobiology at the Cincinnati Children's Hospital Medical Center.


Personal life


Family

Hogenesch was born on May 29, 1967, in
Rotterdam Rotterdam ( , , , lit. ''The Dam on the River Rotte'') is the second largest city and municipality in the Netherlands. It is in the province of South Holland, part of the North Sea mouth of the Rhine–Meuse–Scheldt delta, via the ''"N ...
, Netherlands. He was raised in
Gainesville, Florida Gainesville is the county seat of Alachua County, Florida, Alachua County, Florida, and the largest city in North Central Florida, with a population of 141,085 in 2020. It is the principal city of the Gainesville metropolitan area, Florida, Gaine ...
, by his father Thieo E. Hogen-Esch and his mother Cheryl H. St. George. His parents both work at the
University of Southern California The University of Southern California (USC, SC, or Southern Cal) is a Private university, private research university in Los Angeles, California, United States. Founded in 1880 by Robert M. Widney, it is the oldest private research university in C ...
. His father is a
polymer chemist A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic and ...
, and his mother is a clinical instructor in
psychiatry Psychiatry is the medical specialty devoted to the diagnosis, prevention, and treatment of mental disorders. These include various maladaptations related to mood, behaviour, cognition, and perceptions. See glossary of psychiatry. Initial psych ...
and
behavioral sciences Behavioral sciences explore the cognitive processes within organisms and the behavioral interactions between organisms in the natural world. It involves the systematic analysis and investigation of human and animal behavior through naturalistic o ...
. His brother, Tom Hogen-Esch is a Political Science and Urban Studies professor at Cal State Northridge.


Education

Hogenesch originally received a B.A. in History from the
University of Southern California The University of Southern California (USC, SC, or Southern Cal) is a Private university, private research university in Los Angeles, California, United States. Founded in 1880 by Robert M. Widney, it is the oldest private research university in C ...
in 1989 followed by a B.S. in Biology in 1991. He was inspired to study chronobiology by Joseph Takahashi in the fall of 1992 after learning about the
Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
clock in a lecture. In 1999 Hogenesch completed a Ph.D. in Neuroscience at
Northwestern University Northwestern University is a private research university in Evanston, Illinois. Founded in 1851, Northwestern is the oldest chartered university in Illinois and is ranked among the most prestigious academic institutions in the world. Charte ...
's Chicago campus, studying
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
s with basic helix-loop-helix ( BHLH) and PAS
protein domains In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...
. Hogenesh was mentored by Chris Bradfield, now a professor of
oncology Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ó ...
and the Director of the Molecular and Environmental Toxicology Graduate Program at the University of Wisconsin-Madison. He continued his research on functional genomics as a postdoctoral researcher with Dr.
Steve A. Kay Steve A. Kay is a British-born chronobiologist who mainly works in the United States. Dr. Kay has pioneered methods to monitor daily gene expression in real time and characterized circadian gene expression in plants, flies and mammals. In 2014 ...
at the
Genomics Institute of the Novartis Research Foundation Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
.


Career


Discovery of BMAL1

In March, 1997, Hogenesch was a neuroscience graduate student at
Northwestern University Northwestern University is a private research university in Evanston, Illinois. Founded in 1851, Northwestern is the oldest chartered university in Illinois and is ranked among the most prestigious academic institutions in the world. Charte ...
in the laboratory of Christopher Bradfield, when he discovered five transcription factors in the basic helix-loop-helix-PAS (bHLH-PAS) domain superfamily during his thesis work. These transcription factors were initially named MOP1-5. Hogenesch’s later characterization of MOP3, better known as BMAL1 or ARNTL, revealed in 1998 that its role as a partner of the bHLH-PAS transcription factor
CLOCK A clock or a timepiece is a device used to measure and indicate time. The clock is one of the oldest human inventions, meeting the need to measure intervals of time shorter than the natural units such as the day, the lunar month and the ...
was essential to the function of the mammalian circadian clock. BMAL1 and CLOCK are now the two most well recognized bHLH-PAS domain transcription factors. Later work revealed that ''Bmal1'' is the only clock gene without which the circadian clock fails to function in humans. BMAL1 functions as a positive element in the circadian clock. It forms a heterodimer with CLOCK to initiate transcription of target genes that contain E-box sequences, such as Period and Cryptochrome in mice. The BMAL1:CLOCK complex is suppressed by the buildup of the PER:CRY heterodimers. After receiving his Ph.D. in 1999, Hogenesch followed his Ph.D. mentor Christopher Bradfield to the
University of Wisconsin-Madison A university () is an institution of higher (or tertiary) education and research which awards academic degrees in several academic disciplines. Universities typically offer both undergraduate and postgraduate programs. In the United States, the ...
and continued in his lab as a postdoctoral associate. During this time, Hogenesch focused on following up on his Ph.D. work.


Assembling & mRNA characterization of complete mammalian transcriptomes

Later in 1999, he became a postdoctoral associate with
Steve A. Kay Steve A. Kay is a British-born chronobiologist who mainly works in the United States. Dr. Kay has pioneered methods to monitor daily gene expression in real time and characterized circadian gene expression in plants, flies and mammals. In 2014 ...
and
Peter G. Schultz Peter G. Schultz (born June 23, 1956) is an American chemist. He is the CEO and Professor of Chemistry at The Scripps Research Institute, the founder and former director of GNF, and the founding director of the California Institute for Biomedi ...
. Kay was employed by the University of California at San Diego and the
Scripps Research Institute Scripps Research, previously known as The Scripps Research Institute (TSRI), is a nonprofit American medical research facility that focuses on research and education in the biomedical sciences. Headquartered in San Diego, California, the institu ...
, while Schultz was employed at the Scripps Research Institute and was founder and director of The Genomics Institute of the Novartis Research Foundation (GNF) in La Jolla, CA. Hogenesch started work on the human
transcriptome The transcriptome is the set of all RNA transcripts, including coding and non-coding, in an individual or a population of cells. The term can also sometimes be used to refer to all RNAs, or just mRNA, depending on the particular experiment. The t ...
and the
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
characterization of the transcriptomes of humans, mice, and rats, which he would later continue as Director of Genomics at GNF. Hogenesch became the Program Manager of Genomics at GNF in 2000, and remained there until 2004. During his time there, he accomplished the compilation of the complete human transcriptome, and also the mRNA characterization of the human, mouse, and rat transcriptomes. These highly cited works, together cited over 3700 times, have been influential in the field of genome biology. Hogenesch then brought together his work on the human and mouse transcriptomes into a gene atlas, which he made available as a tool for other genome biologists.


Characterizing circadian regulation of transcription

In addition to characterizing transciptomes present in various organisms, Hogenesch has also spent time throughout his career determining which genes were regulated on a circadian schedule. Working with his colleagues he has determined that mRNA in plants, flies, mice, and humans all shows extensive circadian regulation. In mammals up to 43% of all genes are regulated according to a circadian clock. Transcription for circadianly regulated mRNA shows regular peaks in morning and evening, which then has implications for the regulation of drug targets.


Non-coding RNA and functional genomics

In 2004 Hogenesch left California to become a professor and the Director of Genome Technology at The Scripps Research Institute's other location in
West Palm Beach, FL West Palm Beach is a city in and the county seat of Palm Beach County, Florida, United States. It is located immediately to the west of the adjacent Palm Beach, which is situated on a barrier island across the Lake Worth Lagoon The Lake Wort ...
, where he continued his work on transcriptomes. Hogenesch contributed to a study published in 2005 which used new RNAi genetic screening techniques to discover a non-coding RNA (ncRNA) known as NRON. NRON, a repressor of the protein NFAT, is one of the first well characterized examples of a ncRNAs involved in transcription regulation. In 2006, Hogenesch moved to the
Perelman School of Medicine at the University of Pennsylvania The Perelman School of Medicine, commonly known as Penn Med, is the medical school of the University of Pennsylvania, a private research university in Philadelphia, Pennsylvania. Founded in 1765, the Perelman School of Medicine is the oldest medi ...
where he continues to study mammalian circadian clocks and genome function. One of his current research directions includes incorporating research on noncoding RNA, such as siRNA or
hairpin RNA A short hairpin RNA or small hairpin RNA (shRNA/Hairpin Vector) is an artificial RNA molecule with a tight hairpin turn that can be used to silence target gene expression via RNA interference (RNAi). Expression of shRNA in cells is typically acco ...
isolated by combining
forward genetics Forward genetics is a molecular genetics approach of determining the genetic basis responsible for a phenotype. Forward genetics provides an unbiased approach because it relies heavily on identifying the genes or genetic factors that cause a partic ...
and genomic screens. He has used this technique on miRNA to examine signalling and cell survival.


Contributions to the core clock mechanisms and the field of chronobiology

Over the course of his career, Hogenesch has made numerous contributions to the understanding of the core clock mechanisms. He discovered the key proteins ''Bmal1'' (''Arntl''), and ''Bmal2'' early in his career. He was also on the team that discovered ''Rora'' to be an important regulator of ''Bmal1''. ''Rora'' is currently under investigation for a possible connection to
autism The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...
, which may relate to its function as a circadian regulator. Hogenesch has also contributed to the identification of hundreds more genes that modulate circadian rhythms in humans by using genome wide RNAi scanning. More recently, he discovered new clock gene CHRONO using novel computer based
machine learning Machine learning (ML) is a field of inquiry devoted to understanding and building methods that 'learn', that is, methods that leverage data to improve performance on some set of tasks. It is seen as a part of artificial intelligence. Machine ...
techniques to prioritize clock gene candidates. Hogenesch has also contributed to the field by mentored scientists like Satchin Panda and has collaborated with over 25 other scientists on a variety of papers that cover a range of topics including CREB signaling, NF-κB signaling, TRP channels,
melanopsin Melanopsin is a type of photopigment belonging to a larger family of light-sensitive retinal proteins called opsins and encoded by the gene ''Opn4''. In the mammalian retina, there are two additional categories of opsins, both involved in the for ...
signaling, cell type specific splicing, noncoding RNA function, and RNA-seq methods and mapping algorithms.


Applications of scientific achievements


Wikipedia and chronobiology

Hogenesh has pushed for the chronobiology community to create
Wikipedia Wikipedia is a multilingual free online encyclopedia written and maintained by a community of volunteers, known as Wikipedians, through open collaboration and using a wiki-based editing system. Wikipedia is the largest and most-read refer ...
pages about genes through a project called
Gene Wiki The Gene Wiki is a project within Wikipedia that aims to describe the relationships and functions of all human genes. It was established to transfer information from scientific resources to Wikipedia stub articles. The Gene Wiki project also init ...
. The result has been the creation of pages about genes involved in the circadian clock such as ARNTL, as well as pages about chronobiologists like
Ingeborg Beling Ingeborg Beling (1904-1988) was a German Ethology, ethologist from the early 20th century who worked in the field of chronobiology. She studied at the University of Munich under the direction of Karl Von Frisch and is known for her research on the ...
. He has also been instrumental in creating the Gene Atlas. This project uses a database run by Hogenesch called the Circa database that lists time of activity of genes in different tissues. As an open source database, it allows biologists and pharmaceutical researchers to determine the peak time of different genes and mRNA which can then be used to target drug treatments.


Medicinal uses of chronobiology

In October 2014, Hogenesch's discovery that many proteins targeted by drugs experience circadian fluctuations made strides towards chronotherapy treatment. Further research has focused on the timing of drug administration with the goal of optimizing drug efficacy by allowing physicians to prescribe medicine to be taken when it is most effective and least likely to cause side effects.


References


External links


Database of Circadian Genes Run By Hogenesch
{{DEFAULTSORT:Hogenesch, John B. Living people 1967 births American bioinformaticians Chronobiologists American pediatricians People from Gainesville, Florida University of Southern California alumni Northwestern University alumni University of Wisconsin–Madison faculty University of Pennsylvania faculty Dutch emigrants to the United States