User:Macy Calvasina/Richard Palmiter

= Richard Palmiter[ edit] = Richard Palmiter is a notable cellular biologist. He was born in Poughkeepsie, NY and later went on to earn a BA in Zoology from Duke University and a PhD in Biological Sciences from Stanford University. He is employed with the University of Washington where he is a professor of biochemistry and genome sciences. His current research involves developing a deeper understanding of Parkinson’s Disease. His most notable research is a collaboration with Dr. Ralph Brinster where the injected purified DNA into a single-cell mouse embryo, showing transmission of the genetic material to subsequent generations for the first time.

Background and Education[ edit]
Richard Palmiter was born in Poughkeepsie, NY on April 5, 1942. Palmiter earned his Bachelor of Arts in Zoology at Duke University in 1964 followed by a PhD in Biological Sciences from Stanford University in 1968. He has been employed with the University of Washington since 1974. He was appointed as Investigator of the Howard Hughes Medical Institute two years later in 1976. His research is notable in the cell biology community which is evidenced by his funding by the National Institutes of Health and the Michael J. Fox Foundation. He has been a contributing member to the prestigious National Academy of Sciences since 1984. Due to his background education and passions, his work primarily centers around molecular biology and animal physiology. In addition to his research, he is a professor of biochemistry at the University of Washington. [1]

The Regulation of Egg White Production in Laying Hens[ edit]
Palmiter’s research career began with the role of sex steroids and the regulation of the transcription of genes responsible for egg white production in laying hens. This research surrounding the regulation of gene transcription led him and his team to focus more specifically on the regulation and function of metallothionein genes: gene products that bind heavy metals and are believed to have a role in metal homeostasis and resistance to metal toxicity and oxidative damage. This research is notable as his group was the first to clone these specific genes and the group has later gone on to dissect the regulatory elements involved in their expression. His background in zoology allowed him to lead his team to generate mice that make excess metallothionein or mice that are unable to make specific metallothionein proteins as a means of exploring the gene function in animals. [2]

Transgenic Mice Collaboration with Dr. Ralph Brinster[ edit]
Palmiter’s most well-known work involves his studies on making transgenic mice. This research was conducted in a 15-year transcontinental collaboration with Dr. Ralph Brinster at the University of Pennsylvania. These researchers were pioneers in introducing functional genes into the genome of mice, rabbits, sheep, and pigs -- these animals with foreign genes inserted into their genomes are labeled transgenic. Palmiter and Brinster created the ‘super mouse.’  This mouse grew larger than normal as a result of adding a hybrid gene to the mouse genome. The mice carried a growth hormone gene that was controlled by the regulatory elements of the aforementioned metallothionein gene. Prior to their work, the term ‘transgenic’ was virtually unheard of; but after their collaboration, the use of the word in scientific papers has skyrocketed.

DNA sequences important for the restriction of gene expression to specific cell types were discovered due to these newly created transgenic mice. These mice were also used for studying cell transformation and cancer. Palmiter’s research group also uses gene knockout techniques to inactive genes with the primary responsibility of chemical transmitter synthesis that is vital for studying the nervous system development and function. Their research has concluded that noradrenaline is essential for normal maternal behavior and defense against cold stress: mice that cannot generate neuropeptide Y eat and grow normally but they are alcoholic and have a tendency to have epileptic seizures. [3]

Zinc as a Chemical Transmitter[ edit]
Palmiter and his research group have also investigated the role of zinc as a chemical transmitter in the brain. They have discovered that it prevents excessive excitability of the CNS. Mice that do not make dopamine are found to be hypoactive and have no motivation to eat or drink. Despite their lack of thirst or hunger, these mice can be kept alive with pharmacological delivery of L-DOPA or viral gene therapy with vectors that restore L-DOPA synthesis. [4] The group’s recent research has turned to the attempt to enhance understanding of Parkinson’s disease. The underlying cause of PD is a gradual loss of neurons that produce dopamine. Palmiter’s current ideas suggest that the disruption of mitochondrial function and the accumulation of damaged proteins has the potential to lead to the death of dopaminergic neurons. Their current task is developing models to mimic these cellular processes. [5]

Honors and Scientific Legacy[ edit]
Palmiter’s valuable research has contributed greatly to the molecular biology field; therefore, he has received numerous awards and accolades as well as given lectures at notable conferences throughout his career. His lectures include the Vern Chapman lecture in 2004 at the 18th International Mouse Genome Meeting as well as the Wallace Rowe lecture in 1999 at the American Association of Laboratory Animal Sciences 50th Annual Meeting. In 1999 he became a Tyner Eminent Scholar at Florida State University, in 1998 he was distinguished as a Second International Fellow of the Garvan Institute in Sydney, Australia, and in 1988 he was elected to both the National Academy of Sciences and the American Academy of Arts and Sciences. His awards include the Charles-Leopold Mayer Award from the French Academy of Sciences in 1994, the Distinguished Service Award from the US Department of Agriculture in 1989, the New York Academy Award in Biological and Medical Sciences in 1983, and the George Thorn Award from the Howard Hughes Medical Institute in 1982. [X]

Selected Publications[ edit]
·       Bloodgood DW, Hardaway JA, Stanhope CM, Pati D, Pina MM, Neira S, Desai S, Boyt KM, Palmiter RD, Kash TL. Kappa opioid receptor and dynorphin signaling in the central amygdala regulates alcohol intake. Mol. Psychiatry 2020 Feb; [PMID:32099099]

·       Sanchis P, Fernández-Gayol O, Comes G, Escrig A, Giralt M, Palmiter RD, Hidalgo J. Interleukin-6 Derived from the Central Nervous System May Influence the Pathogenesis of Experimental Autoimmune Encephalomyelitis in a Cell-Dependent Manner. Cells 2020 Jan; 9(2). [PMID:32023844]

·       Heymann G, Jo YS, Reichard KL, McFarland N, Chavkin C, Palmiter RD, Soden ME, Zweifel LS. Synergy of Distinct Dopamine Projection Populations in Behavioral Reinforcement. Neuron 2019 Dec; [PMID:31879163]

·       Zhang Z, Zhong P, Hu F, Barger Z, Ren Y, Ding X, Li S, Weber F, Chung S, Palmiter RD, Dan Y. An Excitatory Circuit in the Perioculomotor Midbrain for Non-REM Sleep Control. Cell 2019 May; 177(5):1293-1307.e16. [PMID:31031008]

·       Padilla SL, Perez JG, Ben-Hamo M, Johnson CW, Sanchez REA, Bussi IL, Palmiter RD, de la Iglesia HO. Kisspeptin Neurons in the Arcuate Nucleus of the Hypothalamus Orchestrate Circadian Rhythms and Metabolism. Curr. Biol. 2019 02; 29(4):592-604.e4. [PMID:30744968]

·       Fergani C, Leon S, Padilla SL, Verstegen AM, Palmiter RD, Navarro VM. NKB signaling in the posterodorsal medial amygdala stimulates gonadotropin release in a kisspeptin-independent manner in female mice. Elife 2018 12; 7. [PMID:30565563] [PMCID:PMC6300354]

·       Chen JY, Campos CA, Jarvie BC, Palmiter RD. Parabrachial CGRP Neurons Establish and Sustain Aversive Taste Memories. Neuron 2018 11; 100(4):891-899.e5. [PMID:30344042] [PMCID:PMC6250580]

·       Qiu J, Rivera HM, Bosch MA, Padilla SL, Stincic TL, Palmiter RD, Kelly MJ, Rønnekleiv OK. Estrogenic-dependent glutamatergic neurotransmission from kisspeptin neurons governs feeding circuits in females. Elife 2018 08; 7. [PMID:30079889] [PMCID:PMC6103748]

·       Melief EJ, McKinley JW, Lam JY, Whiteley NM, Gibson AW, Neumaier JF, Henschen CW, Palmiter RD, Bamford NS, Darvas M. Loss of glutamate signaling from the thalamus to dorsal striatum impairs motor function and slows the execution of learned behaviors. NPJ Parkinsons Dis 2018; 4:23. [PMID:30083593] [PMCID:PMC6072777]

·       Padilla SL, Johnson CW, Barker FD, Patterson MA, Palmiter RD. A Neural Circuit Underlying the Generation of Hot Flushes. Cell Rep 2018 07; 24(2):271-277. [PMID:29996088] [PMCID:PMC6094949]

References[ edit]
1.     Richard D. Palmiter, PhD. (n.d.). Retrieved March 4, 2020, from https://www.michaeljfox.org/researcher/richard-d-palmiter-phd

2.     Palmiter, R. D., Brinster, R. L., Hammer, R. E., Trumbauer, M. E., Rosenfeld, M. G., Birnberg, N. C., & Evans, R. M. (1982). Dramatic growth of mice that develop from eggs microinjected with metallothionein-growth hormone fusion genes. Nature, 300(5893), 611–615. https://doi.org/10.1038/300611a0

3.     Palmiter, R., Brinster, R., Hammer, R. et al. Dramatic growth of mice that develop from eggs microinjected with metallothionein–growth hormone fusion genes. Nature 300, 611–615 (1982). https://doi.org/10.1038/300611a0

4.     Cole TB, Wenzel HJ, Kafer KE, Schwartzkroin PA, Palmiter RD. Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene. Proc Natl Acad Sci U S A. 1999;96(4):1716–1721. doi:10.1073/pnas.96.4.1716

5.     Szczypka MS, Rainey MA, Kim DS, et al. Feeding behavior in dopamine-deficient mice. Proc Natl Acad Sci U S A. 1999;96(21):12138–12143. doi:10.1073/pnas.96.21.12138

6.     Faculty. (n.d.). Retrieved March 4, 2020, from https://depts.washington.edu/biowww/pages/faculty-Palmiter.shtml