University of Colorado Boulder
Dr. Han is also a professor of molecular, cellular, and developmental biology at the University of Colorado at Boulder; a member of the Cancer Center at the University of Colorado Health Sciences Center, Denver; and an adjunct professor at the Institute of Developmental Biology and Molecular Medicine of Fudan University, Shanghai.
Functional Analysis of Metabolic Events, Cell Signaling, and Gene Expression During Animal Development and Stress Response
Min Han uses Caenorhabditis elegans and mouse models to study problems related to animal development, stress response, and human disease, applying both genetic and biochemical methods. The current major focus of his lab is the functional impact of lipid variants and metabolic events, as well as roles of noncoding RNAs.
With a serious childhood illness, a poor middle school education, and a first job as a teen working on a farm in rural China, Min Han never even thought about college as a youngster. But in 1978, soon after China's 10-year Cultural Revolution was over, the country resumed university enrollment based on national examinations.
To prepare for the test, Han taught himself mathematics, chemistry, and physics. He did so well, Han was accepted into Peking (Beijing) University. Although he was directed to study biology—not his first choice—Han relished the opportunity and made the most of it. A U.S.-China joint program brought him to America to attend graduate school at UCLA in 1983.
Overcoming the challenges of his early hardships, he said, helped shape him both as a person and as a scientist. As a child he was in and out of hospitals and bedridden for two years and underwent multiple operations, one of which caused his heart to stop for two minutes. Working on the farm also was difficult because his future prospects were obscure. But Han learned to accept life's uncertainty, be adaptable, and take risks—key skills for a researcher. Moreover, when things did not go as he would like, he maintained equanimity, appreciating what the situation offered.
With such life lessons in hand, mentor Michael Grunstein then taught him how to ask important biological questions. The laboratory had been using genetics to investigate how histones, proteins associated with DNA, regulate transcription, or gene expression. At the time, many scientists thought histones merely acted as a physical scaffold for DNA, but did not do much else. Han's thesis provided the first in vivo evidence of histone's significance in gene regulation.
Today, Han continues to explore uncharted areas of nature, where others may fear to tread. He researches very basic issues in biology, focusing mostly on understanding mechanisms that guide development. To do so, he employs the model system Caenorhabditis elegans, a worm about 1 mm in size with approximately 960 cells. In the wild, it lives in the soil; in the laboratory its developmental progression is easily visualized under the microscope because it is translucent.
C. elegans is a valuable tool for scientists because it shares many key characteristics with mammals: Its DNA is packaged into chromosomes and into a nucleus, a large percent of its genes are similar to human genes, and it undergoes developmental stages from embryo to adult. By dissecting the fundamental pathways that determine C. elegans development, Han and others have provided clues to these processes in more sophisticated species, such as humans.
Han first became interested in C. elegans biology as a postdoctoral researcher in Paul Sternberg's lab at the California Institute of Technology in 1988. At the time, scientists were only beginning to use C. elegans to study the genes involved in regulating development. Han's research with Sternberg had shown a hitherto unknown relationship between a C. elegans gene, let-60, which controls the formation of a female genital organ in the worm, and the ras gene, an oncogene. That genes involved in development might also be involved in the uncontrolled cell growth of cancer was a landmark finding.
It is now known that the same ras pathway genes are used in different cell types and at different times for a range of purposes. In fact, Han's laboratory has employed genetic techniques in C. elegans and other biochemical methods to identify many of the proteins in the ras pathway that play a role in how cells communicate with each other, in developmental biology and in cancer.
In recent years, Han and his colleagues have extended their research in areas related to and unrelated to development. For example, his laboratory has characterized key proteins that determine cell nucleus location using C. elegans and mice. "The position of the nucleus is often important for cell development and other functions," Han said. He has characterized how multiple nuclei are anchored in particular cells, such as in mice skeletal muscle cells. His students are now also investigating a group of small RNA molecules, called microRNAs, that control the timing of development.
In the last few years, he also has pursued the phenomenon termed "genetic redundancy," in which a specific cellular function is due to multiple genes. "It's like having two older brothers caring for a young sister," Han explained. "If one brother is gone, the other is still available. But if both are gone, the sister is in trouble." His group searched for "redundant" functions associated with worm versions of human tumor-suppressor genes, such as the retinoblastoma (RB) and PTEN genes. He found these genes collaborate with many other genes in regulating animal growth and development.
In work that initially seemed unrelated to C. elegans development, Han began to study the function of fatty acids inside cells. His group used genetic mutations and a technique called RNA interference to knock out expression of enzymes such as ones called elongases that synthesize different fatty acids inside a cell. They also measured how overall gene expression changed in worms missing the enzyme genes to see what other cellular processes might be affected when the cell is unable to manufacture particular fatty acids. They have shown how a group of rarely studied fatty acids play unexpected important roles in animal development.
In the laboratory, Han encourages his graduate students and postdoctoral fellows to address novel problems and always look for new research directions. Han tries to instill in them a sense of inquisitiveness and daring, teaching by example the lessons that have served him so well in his career.