Academic Background

1977-1982  Brown University, Providence, Rhode Island
Program in Molecular and Cell Biology
Degree:  Ph.D.
Discipline:  Developmental Biology

1974-1975  Rutgers University, New Brunswick, New Jersey
Degree:  M.S.
Discipline:  Human Genetics and Genetic Counseling

1971-1973  Stephens College, Columbia, Missouri
Degree:  B.A., Summa Cum Laude 
Double Major:  Biology and Music

1969-197l  Simmons College
Boston, Massachusetts

Genome Organization and the Functional Relationship of DNA/RNA with Nuclear Structure

Research Interests

Jeanne Lawrence’s research bridges fundamental questions about genome regulation with pursuing the clinical implications of recent advances in the studies of epigenetics. The genome is not a linear entity, but exists as a complex three-dimensional configuration within a highly complex nuclear structure. A major focus of Jeanne’s lab has been to demonstrate and investigate the functional organization of specific human genes and their cognate mRNAs within a highly compartmentalized nuclear structure. In recent years it has become increasingly well appreciated that the nucleus contains a number of non-chromatin “compartments”, enriched in different subsets of RNA metabolic factors. The Lawrence Lab has demonstrated that there is a locus-specific organization of genomic DNA with respect to distinct nuclear compartments, which relates and contributes to gene regulation. Some nuclear structures or bodies, including the specific heterochromatic structures, are involved in genetic diseases. Examples studied in the Lawrence Lab include toxic repeat nuclear RNA foci in myotonic dystrophy or epigenetic defects of heterochromatin in FSH muscular dystrophy. Most recently Jeanne’s work has come to focus most heavily on epigenetic changes to nuclear structure and heterochromatin in human pluripotent stem cells (iPS cells) and in cancer cells or tumors.

A pre-eminent model for early embryonic regulation by heterochromatin formation is the inactivation of the human X-chromosome, where epigenetic changes are manifest cytologically across an entire chromosome. The Lawrence Lab is at the forefront of investigating how a large non-coding RNA can control this whole process. The XIST gene was identified in other labs as a potential key to the X-inactivation process, however the RNA did not encode an open-reading frame. Using powerful molecular cytology approaches developed in the Lawrence Lab, we were able to demonstrate that the XIST gene produced a stable, functional nuclear RNA that actually “paints” the entire inactive X-chromosome, but not the active X chromosome. Spreading of XIST RNA across the chromosome is the first step in transforming it into a heterochromatic state. This established the precedent for a new type of functional nuclear RNA involved in chromatin regulation, and other large non-coding RNAs are also being examined in the Lawrence Lab. Current studies focus on how XIST RNA interacts with the chromosome, and what DNA sequences and chromosomal proteins impact this process, using XIST transgenics and bioinformatics as well as cytological epigenetics. Currently, the Lawrence Lab is also pursuing a novel translational approach for gene therapy that stems from these advances in understanding non-coding RNA and chromosome regulation.

Course Information

In addition to her research, Jeanne B. Lawrence Ph.D.,is also the co-director of the Human Genetics Course at UMass Medical School ,which focuses on the genetic knowledge and concepts which underlies almost every aspect of human health, both in normal function and disease. The course covers chromosomal, single gene, and multifactorial disorders, including quantitative analysis of Mendelian and non-Mendelian inheritance, human cancer genetics, epigenomic regulation and recent developments in human genome research.

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