Posted on: 2013-12-28
DANIELLE N. MANDIKIAN, Ph.D.
(email hidden) (phone hidden)
EDUCATION
University of California - Davis, Ph.D. Biochemistry & Molecular Biology 9/2008-12/2013
University of California - Davis, B.S. Biochemistry & Molecular Biology 2003-2008
RESEARCH EXPERIENCE
Doctoral Research, Laboratory of Dr. James Trimmer, UC Davis: 3/2008 – 12/2013
The Kv2.1 voltage gated potassium channel is widely expressed throughout the mammalian brain where it plays a major role in homeostatic regulation of intrinsic neuronal excitability. While mechanisms for how Kv2.1 is modulated through activity-dependent changes in phosphorylation have been elucidated, little is known of molecular complexes which regulate Kv2.1 in a cell or circuit specific manner. My dissertation work showed that in distinct regions of the mouse brain, Kv2.1 clusters are juxtaposed to clusters of Ryanodine Receptor (RyR) intracellular calcium-release channels and a calcium dependent phosphatase previously shown to regulate Kv2.1. I also showed that stimulation of RyRs lead to changes in Kv2.1 activity. Together these studies reveal that specific neurons in mouse brain have a distinct clustered localization of Kv2.1 that provides a mechanism for coupling intracellular calcium release to phosphorylation-dependent regulation of Kv2.1 function in a circuit specific manner.
Visiting Researcher, Laboratory of Dr. Ryuichi Shigemoto, NIPS, Okazaki, Japan: 6/2012 – 8/2012
As part of an exchange program, I traveled to Japan to learn how to do electron microscopy (EM). I used EM in my dissertation to determine the ultrastructural localization of the Kv2.1 potassium channel and its auxiliary subunit AMIGO-1 in multiple neuron types of the mouse brain. I prepared samples using the immuno-gold pre-embedding technique.
Undergraduate Research Assistant, Laboratory of Dr. Ken Kaplan, UC Davis: 9/2006– 7/2008
The process of cellular division occurs in distinct stages and is highly regulated through dynamic protein interactions. Passenger proteins are thought to play a role in coupling chromosome segregation with cytokinesis. In order to identify which of these passenger proteins are necessary for cytokinesis, I made mutations in passenger proteins expressed in budding yeast. I then analyzed the mutants for defects in cytokinesis using time lapse microscopy and assayed for changes in protein interactions.
Summer Intern IRTA, Laboratory of Dr. Jay Chiorini, National Institutes of Health:
6– 9/2007
Viral based gene therapies are promising treatment options for a number of human diseases. One important challenge that must be addressed is the expression rate of the protein introduced by the viral vector. In an effort to improve expression rates for Adeno Associated Viral (AAV) constructs designed to treat Hemophilia and Sjögren's Syndrome, I used site directed mutagenesis for codon optimization. There is a redundancy in which DNA sequences (codons) will translate for specific amino acids, but the abundances of redundant codons are not equal. Mutations that swap for more abundant codons result in higher expression rates and improved the efficacy of the AAV constructs.
Summer Intern UARC, Laboratory of Dr. Jun Li, NASA AMES:
6– 9/2005 & 2006
Deep brain stimulation is a surgical procedure used to treat Parkinson's Disease, but often leads to lesions along the length of the implantation. In order to minimize damage and increase sensitivity of the electrode used for stimulation, a neural interface carbon nanoelectrode biosensor was designed. I used fast scan cyclic voltammetry to look at factors to improve detection capabilities such as various dielectrics and thin films used for bio-support and small molecule filtration.
TEACHING & MENTORING
Teaching Assistant, Biochemistry Laboratory, UC Davis: 9/2010 – 12/2010
Tutor, Online Chemistry and Biology Tutor, Fresno City College: 2007-2008
Teaching Assistant, GRASP, Fresno City College: 2004-2006
Tutor, Fresno City College: 2003-2006
PUBLICATIONS
Cell type specific spatial and functional coupling between mammalian brain Kv2.1 K+ channels and ryanodine receptors. Mandikian, Bocksteins, Parajuli, Cerda, Evans, Shigemoto and Trimmer. Submitted to Journal of Neuroscience in November 2013 and is currently in review.
Deletion of the homeostatic suppressor Kv2.1 leads to neuronal and behavioral hyperexcitability. Speca, Ogata, Mandikian, Wiler, Eum, Wenzel, Doisy, Matt, Campi, Golub, Nerbonne, Hell, Trainor, Sack, Schwartzkroin and Trimmer. Submitted to Genes, Brain and Behavior in November 2013 and is currently in review.
A SUMO-Phospho tag team for wrestling with potassium channel gating. Mandikian D, Cerda O, Sack JT, Trimmer JS.. J Gen Physiol. 2011 May;137(5):435-9.
Adeno-associated virus type 12 (AAV12): a novel AAV serotype with sialic acid- and heparan sulfate proteoglycan-independent transduction activity. Schmidt M, Voutetakis A, Afione S, Zheng C, Mandikian D, Chiorini JA..J Virol. 2008 Feb;82(3):1399-406.
ABSTRACTS & PRESENTATIONS
Cobb MM, Bishop H, Mandikian D, Trimmer JS. Expression and localization of Kv2 channels and their AMIGO auxiliary subunits. (Poster) Presented at the 2013 Annual Meeting of the Society for Neuroscience; San Diego, CA.
D. N. Mandikian, , O. Cerda, A. Evans, D. Schneider, J. S. Trimmer. Association and colocalization of plasma membrane Kv2.1 voltage-gated potassium channels with intracellular ryanodine receptor calcium-release channels. (Poster) Presented at the 2012 Annual Meeting of the Society for Neuroscience; New Orleans,
Mandikian. The role of the HSP90 chaperone in coordinating anaphase events. (Talk) Presented in the 2007 and 2008 Undergraduate Research Conference, UC Davis; Davis, CA.
Mandikian, T.B. Nguyen-Vu, J. Li. Development of Dopamine Detection with Carbon Nanofiber Nanoelectrode Array. (Poster) Presented at the 2005 Summer Internship Research Conference, NASA Ames Research Center; Mountain View, CA.
RESEARCH & TRAINING GRANTS
Molecular and Cellular Biology Training Grant: 2009-2011
Competitive National Institutes of Health Funded Training Grant. Grant covered all tuition and stipend.
TECHNICAL SKILLS
Acute Seizure Induction, Blue Native PAGE, Cell culture, ELISA, Fast-Scan Cyclic Voltammetry, Immunohistochemistry, Immunoprecipitation, Light Micrcoscopy, Light Spectroscopy, Monoclonal Antibody Production & Screening, Murine Animal Models, Quantitative Mass Spectrometry, Time Lapse Microscopy, Tissue Collection, Trans-cardial Perfusion, Transmission Electron Microscopy, Western Blotting, Yeast & Bacterial Genetics.
REFERENCES
James Trimmer, Ph.D. (email hidden)
Department of Neurobiology, Physiology and Behavior
University of California, One Shields Avenue, Davis CA 95616 (phone hidden)
David Speca, Ph.D. (email hidden)
Department of Neurobiology, Physiology and Behavior
University of California, One Shields Avenue, Davis CA 95616 (phone hidden)
Ken Kaplan, Ph.D. (email hidden)
Department of Molecular and cellular Biology
University of California, One Shields Avenue, Davis CA 95616 (phone hidden)