John M. Parant, Ph.D.

John_Parant

Assistant Professor

Education:

BS: Florida Institute Of Technology, Melbourne, Florida

Ph.D: University of Texas Graduate School of Biomedical Science, Houston, Texas

Postdoc: University of Utah, Salt Lake City, Utah

 

Research Interests:     

The overall focus of my lab is to understanding the regulation as well as cause of genomic instability in cancer and other diseases. Genomic instability is the number one prognostic indicator of tumor initiation, as well as the leading cause of miscarriages in women. Understanding these signatures are both useful as prognostic indicators as well as therapeutic targets. For many years I have been working on the regulation of the tumor suppressor p53, and its influence on genomic instability.  In addition, I have begun studies that shown that cohesion molecules, important for sister chromatic cohesion, are involved in preventing chromosomal instability, in particular aneuploidy, a key signature of cancers.

I have taken a two prong approach: 1) model familial human diseases with genomic instability in experimentally amenable organisms through gene knockdown and ask key questions about function and mechanism. 2) Design genetic screens to identify genes involved in various aspects of genomic instability.  We use both zebrafish and mouse to achieve these goals, although initial studies will focus on zebrafish. For my interests, zebrafish are advantageous since they have large cohort size [allowing powerful statistical analysis in tumor screens as well as embryonic analysis], have almost the complete complement of the human genome [reciprocate the complexity of the human genome], ability to perform powerful unbiased genetic screens [identify novel disease genes and pathways], allow in-vivo observation of chromosomal dynamics in the whole live organism [often the in-vitro phenotype or fixed tissue phenotype do not reciprocate the in-vivo live phenotype], and perform in-vivo drug screens on whole zebrafish embryos [circumventing DNA heterogeneity, drug toxicity and uptake issues often associated with in-vivo environments].

We also have a technology aspect to the lab. We have been developing the use of HRMA (high resolution Melting Curve analysis), initially to genotype mutant animals and now to perform mutation scanning in disease genes as well as mapping phenotypic mutants.

 

Key Publications:

Parant, J., Chavez-Reyes, A., Little, N.A., Yan, W., Reinke, V., Jochemsen, A.G., Lozano, G. Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a non-overlapping pathway with MDM2 to regulate p53. (2001) Nature Genetics 29(1), 92-95.

Liu G., Parant J. M., Lang G., Chau P., Chavez-Reyes A., El-Naggar A.,K.,  Multani A.,  Chang S., and Lozano G. Chromosome stability, in the absence apoptosis, is critical for suppression of tumorigenesis in Trp53 mutant mice. (2004) Nature Genetics 36(1) 63-8

Lang G.A., Iwakuma T., Suh Y.A., Liu G., Rao V.A., Parant J.M., Valentin-Vega Y.A., Terzian T., Caldwell L.C., Strong L.C., El-Naggar A.K., Lozano G. Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. (2004) Cell: 119(6):861-72.

Parant J.M*., Sasai K.*, Brandt M.E., Carter J., Adams H.P., Stass S.A., Killary A.M., Katayama H., Sen S. Aurora Targeted disruption of Aurora A causes abnormal mitotic spindle assembly, chromosome misalignment and embryonic lethality. (2008) Oncogene 27(29):4122-7. *coauthors

Parant J.M., George S.A., Pryor R., Wittwer C. and Yost H.J. A rapid and efficient method of genotyping zebrafish mutants. (2008) Dev Dyn., 238(12):3168-74.

Parant J.M., George S.A., Holden J.A., and Yost H. J. Genetic modeling of Li-Fraumeni syndrome in zebrafish. (2010) Dis Model Mech., 3(1-2):45-56.

Parant J.M., Amsterdam A., Hopkins N., and Yost H.J. p53 dependent apoptosis, mitotic delay, and genomic instability in a zebrafish model of Roberts syndrome. In preparation.

Full Publication List:

 Pubmed  


To contact Dr. Parant:

Department of Pharmacology and Toxicology
UAB School of Medicine
1670 University Boulevard
VH 252Birmingham, AL 35294-0019
Phone: (205) 975-8469
Fax: (205) 934-8240
E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.