Bruce Lahn is a Chinese-born American geneticist. Lahn came to the U.S. from China to continue his education in the late 1980s.
He is the William B. Graham professor of
Human Genetics
Human genetics is the study of inheritance as it occurs in Human, human beings. Human genetics encompasses a variety of overlapping fields including: classical genetics, cytogenetics, molecular genetics, biochemical genetics, genomics, populatio ...
at the
University of Chicago
The University of Chicago (UChicago, Chicago, or UChi) is a Private university, private research university in Chicago, Illinois, United States. Its main campus is in the Hyde Park, Chicago, Hyde Park neighborhood on Chicago's South Side, Chic ...
. He is also the founder of the Center for Stem Cell Biology and Tissue Engineering at
Sun Yat-sen University
Sun Yat-sen University (; SYSU) is a public university in Guangzhou, Guangdong, China. It is affiliated with the Ministry of Education, and co-funded by the Ministry of Education, SASTIND, and Guangdong Provincial Government. The university is p ...
in
Guangzhou
Guangzhou, Chinese postal romanization, previously romanized as Canton or Kwangchow, is the Capital city, capital and largest city of Guangdong Provinces of China, province in South China, southern China. Located on the Pearl River about nor ...
,
China
China, officially the People's Republic of China (PRC), is a country in East Asia. With population of China, a population exceeding 1.4 billion, it is the list of countries by population (United Nations), second-most populous country after ...
. Lahn currently serves as the chief scientist of VectorBuilder, Inc.
Lahn's honors include the
TR100
The Innovators Under 35 is a peer-reviewed annual award and listicle published by ''MIT Technology Review'' magazine, naming the world's top 35 innovators under the age of 35. at ''Technology Review'' with lists of winners at technologyreview.com
...
Award from ''
Technology Review
''MIT Technology Review'' is a bimonthly magazine wholly owned by the Massachusetts Institute of Technology. It was founded in 1899 as ''The Technology Review'', and was re-launched without "''The''" in its name on April 23, 1998, under then pu ...
'' magazine, the
Merrill Lynch
Merrill Lynch, Pierce, Fenner & Smith Incorporated, doing business as Merrill, and previously branded Merrill Lynch, is an American investment management and wealth management division of Bank of America. Along with BofA Securities, the investm ...
Forum Global Innovation Award, the
Burroughs Wellcome
GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...
Career Award, and a
Searle Scholarship. He was also named to the 40-Under-40 list by
''Crain’s Chicago Business'' magazine,
Forbes
''Forbes'' () is an American business magazine founded by B. C. Forbes in 1917. It has been owned by the Hong Kong–based investment group Integrated Whale Media Investments since 2014. Its chairman and editor-in-chief is Steve Forbes. The co ...
China 100 Most Influential Chinese Worldwide, and PharmaVoice 100 Top Industry Leaders. Lahn received his
B.A.
A Bachelor of Arts (abbreviated B.A., BA, A.B. or AB; from the Latin ', ', or ') is the holder of a bachelor's degree awarded for an undergraduate program in the liberal arts, or, in some cases, other disciplines. A Bachelor of Arts degree ...
in
General Biology from
Harvard University
Harvard University is a Private university, private Ivy League research university in Cambridge, Massachusetts, United States. Founded in 1636 and named for its first benefactor, the History of the Puritans in North America, Puritan clergyma ...
and his Ph.D. from the
Massachusetts Institute of Technology
The Massachusetts Institute of Technology (MIT) is a Private university, private research university in Cambridge, Massachusetts, United States. Established in 1861, MIT has played a significant role in the development of many areas of moder ...
in the lab of
David C. Page. From 2000 to 2012, Lahn was a
Howard Hughes Medical Institute
The Howard Hughes Medical Institute (HHMI) is an American non-profit medical research organization headquartered in Chevy Chase, Maryland with additional facilities in Ashburn, Virginia. It was founded in 1953 by Howard Hughes, an American busin ...
Investigator.
His previous research specialized in
human genetics
Human genetics is the study of inheritance as it occurs in Human, human beings. Human genetics encompasses a variety of overlapping fields including: classical genetics, cytogenetics, molecular genetics, biochemical genetics, genomics, populatio ...
and
evolutionary genetics
Population genetics is a subfield of genetics that deals with genetic differences within and among populations, and is a part of evolutionary biology. Studies in this branch of biology examine such phenomena as adaptation, speciation, and popu ...
, especially human sex chromosome evolution and the genetic basis that underlies the evolutionary expansion of the
human brain
The human brain is the central organ (anatomy), organ of the nervous system, and with the spinal cord, comprises the central nervous system. It consists of the cerebrum, the brainstem and the cerebellum. The brain controls most of the activi ...
. Lahn's current research interests include
stem cell biology,
epigenetics
In biology, epigenetics is the study of changes in gene expression that happen without changes to the DNA sequence. The Greek prefix ''epi-'' (ἐπι- "over, outside of, around") in ''epigenetics'' implies features that are "on top of" or "in ...
and
biotechnology
Biotechnology is a multidisciplinary field that involves the integration of natural sciences and Engineering Science, engineering sciences in order to achieve the application of organisms and parts thereof for products and services. Specialists ...
.
[Lahn's Lab Website](_blank)
Biography
Bruce Lahn is a Chinese-born American scientist. He is the founder and chief scientist of VectorBuilder, a global leader in gene delivery solutions.
In the past he has studied human genetics and evolutionary genetics. His main objective with previous studies was to study the evolution of human sex chromosomes and the underlying basis for the growth of the human brain. Lahn is currently doing a wide spread of stem cell research as well as working with epigenetics.
Lahn's previous research has led to the hypothesis that the Neanderthals contributed to evolution of the human brain's size.
Lahn is currently working to contribute a better understanding of the widespread use of stem cells to the science world.
Contributions to science
Lahn's research covers several areas including
human genetics
Human genetics is the study of inheritance as it occurs in Human, human beings. Human genetics encompasses a variety of overlapping fields including: classical genetics, cytogenetics, molecular genetics, biochemical genetics, genomics, populatio ...
,
evolutionary biology
Evolutionary biology is the subfield of biology that studies the evolutionary processes such as natural selection, common descent, and speciation that produced the diversity of life on Earth. In the 1930s, the discipline of evolutionary biolo ...
,
sex chromosome biology, and
stem cell biology
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...
.
Stem cell biology
Lahn’s team showed that the
neural stem cell
Neural stem cells (NSCs) are self-renewing, multipotent cells that firstly generate the radial glial progenitor cells that generate the neurons and glia of the nervous system of all animals during embryonic development. Some neural progenitor st ...
gene
Nestin is essential in
neurogenesis
Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). This occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells ( ...
. He and his colleagues at Sun Yat-sen University explored the use of
suicide gene
In the field of genetics, a suicide gene is a gene that will cause a cell to kill itself through the process of apoptosis (programmed cell death). Activation of a suicide gene can cause death through a variety of pathways, but one important cellul ...
s to control
tumorigenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abn ...
in
stem-cell therapy
Stem-cell therapy uses stem cells to treat or prevent a disease or condition. , the only FDA-approved therapy using stem cells is hematopoietic stem cell transplantation. This usually takes the form of a bone marrow or peripheral blood stem cel ...
, and the potential of stem
Leydig cell
Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). They are polyhedral ...
s in treating testicular dysfunctions. By transplanting
embryonic stem cell
Embryonic stem cells (ESCs) are Cell potency#Pluripotency, pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-Implantation (human embryo), implantation embryo. Human embryos reach the blastocyst stage 4� ...
s into
blastocyst embryos, his group created
chimeric animals between two divergent
mammals
A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle e ...
, ''
Apodemus
''Apodemus'' is a genus of Muridae, murid (true mice and rats) containing the field mice as well as other well-known species like the wood mouse and the yellow-necked mouse. The name is unrelated to that of the ''Mus (genus), Mus'' genus, instead ...
'' and
''Mus'', showcasing for the first time that evolutionarily divergent species still possessed highly compatible developmental programs. It also suggested the feasibility of growing organs from human stem cells in animal bodies for human
transplantation, which has become an active area of research today.
Molecular evolution
Using
molecular evolution
Molecular evolution describes how Heredity, inherited DNA and/or RNA change over evolutionary time, and the consequences of this for proteins and other components of Cell (biology), cells and organisms. Molecular evolution is the basis of phylogen ...
analysis, Lahn's team discovered a strong correlation between background
mutation rate
In genetics, the mutation rate is the frequency of new mutations in a single gene, nucleotide sequence, or organism over time. Mutation rates are not constant and are not limited to a single type of mutation; there are many different types of mu ...
in mammals and
fixation rate of
nonsynonymous substitution
A nonsynonymous substitution is a nucleotide mutation that alters the amino acid sequence of a protein. Nonsynonymous substitutions differ from synonymous substitutions, which do not alter amino acid sequences and are (sometimes) silent mutations. ...
s that alter
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
sequences. It supports the controversial idea that mutation rate can itself evolve, namely, mutation rates in different genes of a species can be tweaked by
natural selection
Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the Heredity, heritable traits characteristic of a population over generation ...
toward different optimal levels, with low mutation rates adopted in genes unlikely to benefit from nonsynonymous substitutions, while high mutation rates adopted in rapidly evolving genes likely to benefit from nonsynonymous substitutions. Lahn’s group developed a methodology combining
phylogenetic analysis
In biology, phylogenetics () is the study of the evolutionary history of life using observable characteristics of organisms (or genes), which is known as phylogenetic inference. It infers the relationship among organisms based on empirical data ...
with
protein structural analysis to examine the coevolution of interacting
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
residues within proteins, which detected strong signals of interacting-residue coevolution in mammalian
proteome
A proteome is the entire set of proteins that is, or can be, expressed by a genome, cell, tissue, or organism at a certain time. It is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. P ...
s and revealed how physicochemical properties of the interactions impact this coevolution.
Human evolutionary genetics
Lahn worked on several topics in
human and primate evolutionary genetics. His group found that
SEMG2, encoding a major structural component of
semen
Semen, also known as seminal fluid, is a bodily fluid that contains spermatozoon, spermatozoa which is secreted by the male gonads (sexual glands) and other sexual organs of male or hermaphrodite, hermaphroditic animals. In humans and placen ...
, experienced faster evolution in primate species of high
female promiscuity
Promiscuity tends to be frowned upon by many societies that expect most members to have committed, long-term relationships.
Among women, as well as men, inclination for sex outside committed relationships is correlated with a high libido; howeve ...
, showcasing the importance of
sexual selection
Sexual selection is a mechanism of evolution in which members of one sex mate choice, choose mates of the other sex to mating, mate with (intersexual selection), and compete with members of the same sex for access to members of the opposite sex ...
in driving the evolution of
reproductive genes. Lahn’s team observed
accelerated evolution
''Accelerated Evolution'' is the sixth studio album by Canadian musician Devin Townsend, released in 2003. The album, written and produced by Townsend, was a mix of musical styles from alternative rock to hard rock to progressive metal. Townsend, ...
of
nervous system
In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...
genes in primates and especially the human lineage, which may underlie the expanded
cognitive capacity
Cognitive skills are skills of the mind, as opposed to other types of skills such as motor skills, social skills or life skills. Some examples of cognitive skills are literacy, self-reflection, logical reasoning, abstract thinking, critical thinki ...
in humans. They showed that two brain size genes,
ASPM and
Microcephalin (MCPH1), whose
null mutations lead to
microcephaly (small head due to reduced brain size), experienced accelerated evolution in the primate lineage leading to humans, suggesting roles in the enlargement of the human brain. They further showed that in each of these two genes, a newly arisen
haplotype (DNA sequence variant) underwent rapid
selective sweep
In genetics, a selective sweep is the process through which a new beneficial mutation that increases its frequency and becomes fixed (i.e., reaches a frequency of 1) in the population leads to the reduction or elimination of genetic variation amon ...
in recent human history because it was favored by strong
positive selection
In population genetics, directional selection is a type of natural selection in which one extreme phenotype is favored over both the other extreme and moderate phenotypes. This genetic selection causes the allele frequency to shift toward the ...
. The sweep started about 5,800 years ago for ASPM and about 37,000 years ago for MCPH1, and reached high frequencies in some human populations today.
They further showed that the selectively favored haplotype of MCPH1 bore a high degree of sequence difference from other variants of the gene, suggesting that it
introgressed
Introgression, also known as introgressive hybridization, in genetics is the transfer of genetic material from one species into the gene pool of another by the repeated backcrossing of an interspecific hybrid with one of its parent species. Introg ...
into humans from an
archaic ''Homo'' species (
Neanderthal
Neanderthals ( ; ''Homo neanderthalensis'' or sometimes ''H. sapiens neanderthalensis'') are an extinction, extinct group of archaic humans who inhabited Europe and Western and Central Asia during the Middle Pleistocene, Middle to Late Plei ...
s being one possibility) through
interbreeding with humans, and that this introgression might have contributed to human brain development. Later studies found some association of the positively selected haplotypes of ASPM and MCPH1 with tonal language and brain volume in humans, but association with mental abilities has not been found. The MCPH1 haplotype was not found in the individuals used to prepare the first draft of the Neanderthal genome,
[
] suggesting that it might have introgressed from a different archaic ''Homo'' lineage. Lahn's research provoked controversy due to the finding that the positively selected variants of ASPM and MCPH1 had spread to higher frequencies in some parts of the world than in others (for ASPM, it is higher in Europe and surrounding regions than other parts of the world; for MCPH1, it is higher outside sub-Saharan Africa than inside).
Lahn emphasized the importance of scientific curiosity over political implications,
and advocated the moral position that human genetic diversity should be embraced and celebrated as among humanity's great assets.
Sex chromosome function and evolution
Working with David Page, Lahn uncovered many new genes on the human
Y chromosome
The Y chromosome is one of two sex chromosomes in therian mammals and other organisms. Along with the X chromosome, it is part of the XY sex-determination system, in which the Y is the sex-determining chromosome because the presence of the ...
, and showed that human Y genes fall into two categories: widely expressed
housekeeping gene
In molecular biology, housekeeping genes are typically constitutive genes that are required for the maintenance of basic cellular function, and are expressed in all cells of an organism under normal and patho-physiological conditions. Although ...
s with
homologues on the
X chromosome
The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...
that escape
X-inactivation
X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into ...
, and genes expressed only in the
testis
A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is Homology (biology), homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of Androgen, androgens, p ...
and lacking X homologues.
This showed that the human Y is not as gene poor as predicted by the degenerate Y hypothesis., as it retained important housekeeping genes that resisted degeneration and also acquired genes specializing in
spermatogenesis
Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testicle. This process starts with the Mitosis, mitotic division of the stem cells located close to the basement membrane of ...
.
Their further analysis of Y genes with X homologues revealed the evolutionary history of the human
sex chromosome
Sex chromosomes (also referred to as allosomes, heterotypical chromosome, gonosomes, heterochromosomes, or idiochromosomes) are chromosomes that
carry the genes that determine the sex of an individual. The human sex chromosomes are a typical pair ...
s.
It dates back to about 300 million years ago when a
reptile-like ancestor of mammals acquired a new gene,
SRY
Sex-determining region Y protein (SRY), or testis-determining factor (TDF), is a DNA-binding protein (also known as gene-regulatory protein/transcription factor) encoded by the ''SRY'' gene that is responsible for the initiation of male sex ...
, on one of a pair of identical
autosome
An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosomes ...
s. This gene triggered male development, marking the emergence of sex chromosomes with the SRY-bearing chromosome became the Y while the other chromosome of the previous autosome pair became the X. It also marked the evolutionary switch from
temperature-dependent sex-determination system still present in reptiles today to the
XY chromosomal sex-determination system in mammals. When X and Y first emerged, they were matched in sequence just like between any pair of autosomes except for the SRY gene that was present on the Y but absent on the X. Over time, however, the Y degenerated in several episodes, each involving the sudden suppression of
recombination (DNA exchange) across a large segment between X and the Y during male
meiosis
Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...
, likely due to
inversion
Inversion or inversions may refer to:
Arts
* ''Inversion'' (artwork), a 2005 temporary sculpture in Houston, Texas
* Inversion (music), a term with various meanings in music theory and musical set theory
* ''Inversions'' (novel) by Iain M. Bank ...
on the Y, which subsequently led to genes in the affected region of the Y to decay,
a process hypothesized to be driven by
Muller’s ratchet
In evolutionary genetics, Muller's ratchet (named after Hermann Joseph Muller, by analogy with a ratchet effect) is a process which, in the absence of recombination (especially in an asexual population), results in an accumulation of irreversible ...
that operates on nonrecombining regions of the genome. The X maintained its function because it could still recombine in females. This eventually led to highly divergent sequence and function between the human X and Y chromosomes seen today.
Gene delivery technologies
Lahn worked on
gene delivery
Gene delivery is the process of introducing foreign genetic material, such as DNA or RNA, into host cells. Gene delivery must reach the genome of the host cell to induce gene expression. Successful gene delivery requires the foreign gene deliver ...
technologies as the chief scientist of VectorBuilder. Lahn's group developed the miniVec system of miniaturized
plasmid
A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria and ...
backbone to enhance plasmid function, manufacturability and clinical safety. His team reported that nearly half of the plasmids constructed in laboratories around the world contained design or sequence errors, sparking discussions in the
life sciences
This list of life sciences comprises the branches of science that involve the scientific study of life – such as microorganisms, plants, and animals including human beings. This science is one of the two major branches of natural science, ...
community on the need for community-wide standards to uphold the quality of lab-made plasmids that are a workhorse tool in research and medicine.
Contributions to biotechnology industry
Lahn is active in the
biotechnology
Biotechnology is a multidisciplinary field that involves the integration of natural sciences and Engineering Science, engineering sciences in order to achieve the application of organisms and parts thereof for products and services. Specialists ...
industry as a serial entrepreneur and a developer of new tools and technologies.
He is the founder and chief scientist of the
multinational corporation
A multinational corporation (MNC; also called a multinational enterprise (MNE), transnational enterprise (TNE), transnational corporation (TNC), international corporation, or stateless corporation, is a corporate organization that owns and cont ...
VectorBuilder, a global leader in gene delivery solutions.
The company was established in 2014, reached
unicorn
The unicorn is a legendary creature that has been described since Classical antiquity, antiquity as a beast with a single large, pointed, spiraling horn (anatomy), horn projecting from its forehead.
In European literature and art, the unico ...
status in 2022, and is a recipient of the Biotech Breakthrough Award. Lahn led the creation of Vector Design Studio, an online software platform from VectorBuilder for the intuitive design of
gene delivery vectors, allowing researchers with limited molecular biology background to gain access to complex vectors.
He is also the architect of VectorBee, a desktop
genetic engineering software for viewing, editing and analyzing DNA and protein sequences.
Lahn is the founder of Cyagen, a provider of genetically modified rodent models for research.
References
External links
Alumni pageat the
Howard Hughes Medical Institute
The Howard Hughes Medical Institute (HHMI) is an American non-profit medical research organization headquartered in Chevy Chase, Maryland with additional facilities in Ashburn, Virginia. It was founded in 1953 by Howard Hughes, an American busin ...
.
*
*
*
{{DEFAULTSORT:Lahn, Bruce
1969 births
Living people
American geneticists
Chinese emigrants to the United States
Harvard University alumni
Howard Hughes Medical Investigators
Massachusetts Institute of Technology alumni
People involved in race and intelligence controversies
University of Chicago faculty