Dejan

Budimirovic

,

MD

Education

Dr Budimirovic's earned his undergraduate degree from a pre-medical program and his medical degree from Belgrade University. He graduated magna cum laude and achieved dozens of awards and honors as the top student in the Class of 1987. One of his most notable honors was the extraordinary opportunity he was given to complete his medical internship with the University Hospitals in Belgrade. He then completed residencies at Belgrade, Harvard, and New York Universities. He also completed postgraduate study in biological psychiatry. In short, over the past 20 years, Dr. Budimirovic has steadily solidified his clinical, research, and educational experience at Harvard, New York, Yale, and Johns Hopkins Universities, respectively.

Dejan's commitment to his academic career is enduring. He had an entry-level job at Yale as a full-time assistant professor and co-director, then he spent one year as the medical director of children’s psychiatric unit, and this has been followed by a now already 12-year tenure at the Johns Hopkins School of Medicine and the JHMI at the rank of full-time faculty-assistant professor. At the Institute, his clinical and research expertise comes from a very large pool (~500) of patients with and without developmental disabilities (i.e., ~>50% carry the clinical diagnosis of autism spectrum disorder (ASD);>100 carry medical/genetic diagnosis of fragile X associated disorders-FXD). Dejan has significantly contributed to the expansion of clinical and research activities at the Fragile X Clinic, and subsequently CTU that was established under the leadership of Michael Johnston, MD, Chief Medical Officer and Executive Vice President of the Institute. Namely, in February of 2012, Dr Budimirovic was promoted to serve as Medical Director of the Institute's Fragile X Clinic, a role that he shares with a colleague from the Department of Neurogenetics.

Specifically, as the fragile X clinic's leader, clinician, and the only co-Investigator at the time, he has recruited and retained more than two-dozen participants. Such initial achievement was critical to establish the thriving CTU. Upon arrival of Prof dr Robert L. Findling, Leonard and Helen R. Stulman Endowed Professor in Child and Adolescent Psychiatry and Director, Bob's stature and leadership has enabled Dejan to expand his co-Investigator's effort to over 40 clinical trials to date as the main co-Investigator not only in the field of pediatric, and adult FXS but also in idiopathic ASD and other areas (i.e., ADHD).

Dr Budimirovic has been described as a compassionate, talented and skillful physician-developmental neuropsychiatrist with growing and now nationally recognized expertise in the field of FXD and ASD, who has steadily contributed to the Institute's CTU and other goals and objectives of the Institute. Dr. Budimirovic is board certified by the American Board of Psychiatry and Neurology in adult, child, and adolescent psychiatry, and has been re-certified in child and adolescent psychiatry with excellent-outstanding grades. Since 1999, he has been an active member of the American Academy of Child and Adolescent Psychiatry, and a former member of the American Psychiatric and the American Medical Associations.

Research

Dr Budimirovic has steadily contributed to the Fragile X Research Program at the Kennedy Krieger Institute as a child neuropsychiatrist and the main co-Investigator physician. His initial research activities have focused on characterizing social behavior determinants of ASD status in Fragile X Syndrome (FXS) (Budimirovic et al., 2006; Kaufmann et al., 2008; Budimirovic and Kaufmann, 2011). Such effort has generated a meaningful model that has contributed to identifying a factored FXS-specific Social Avoidance-Indifference structure.

The findings were then replicated by refactoring the ABC-C for FXS (ABC-CFX) through a multi-site of the Consortium's collaboration using a sample that was 10-times larger (Sansone et al., 2012). Defining the FXS-specific factor structure (ABC-CFX Social Avoidance) has since been relevant to a series of unfolding clinical trials in FXS, and ASD. To advance the understanding of the pathophysiology of antipsychotic-induced hyperprolactinemia, Dejan have collaborated with the Section on Cellular Signaling at NICHD led by Stanko Stojilkovic, PhD. He led all aspects of a fruitful study of cellular mechanisms underlying prolactin-related effects of paliperidone and aripiprazole on lactotroph function as a senior author that was published in Nature Scientific Report (Kucka et al., 2015).

The study showed for the first time that dopamine receptors in lactotrops exhibit small intrinsic (in the absence of ligand occupancy) activity and that binding of paliperidone silences such activity, leading to enhanced coupling of electrical activity and prolactin secretion.While paliperidone effectively blocks the dopamine action in the lactotrops, in contrast, aripiprazole normalizes the secretory output of the lactotrops independently of dopamine levels by clamping the calcium–secretion coupling. Since 2012, Dr Budimirovic has been a member of the Consortium’s Clinical and Clinical Trials Committee. Furthermore, Dejan has been the PI for the Institute on ongoing FXS-related projects in humans funded by the NIH and the CDC, respectively. The CDC has funded the Fragile X Clinical and Research Consortium’s major database projects.

As the PI for the Institute Dr. Budimirovic remains an active member on several of the FXCRC (database-CDC funded renewed Data Interest Groups such as Cognition/Behavior/Sleep and Psychopharmacology-Behavior. In addition, over the last years, he has been either the PI, co-PI or co-Investigator on half a dozen unfunded grant applications. Dr Budimirovic has been also selected as a DoD study sections reviewer in the field of FXS and ASD. Further recognized by his peers in the field, in 2014 he led the Consortium Clinical Practices Committee’s consensus document titled ‘ASD in FXS’ featured on the National Fragile X Foundation (NFXF) website, http://www.fragilex.org/2014/support-and-resources/fragile-x-syndrome-and-autism-spectrum-disorder-similarities-and-differences/; and recently, he led an effort among renewed experts in the field on an invited manuscript re: tools to measure outcomes of clinical trials in FXS. Since 2011, Dejan has initiated and established all year long a well-accepted and now popular clinical tutorial.

He primarily teaches undergraduate students majoring in neuroscience from Johns Hopkins University Homewood Campus on basic clinical features of ASD and FXD. In order to disseminate knowledge in the field of fragile X and ASD, he encourages, facilitates, and edits writings of his clinical tutorial students. Dr Budimirovic's mentorship effort has resulted that his undergraduate student was recently awarded with one year NIH Undergraduate Scholarship Program (aspiring physician-scientist) and that his predoctoral fellow received a fund ($25, 000) by the Autism Science Foundation.

Furthermore, Dr Budimirovic has also been a committed advocate at the Capitol Hill for the fragile X cause, which further strengthen his ties in the mid-Atlantic region with fragile X parent-support groups, and nationally through the NFXF. Next, as the PI on an investigator-initiated now NIH funded study, Dr. Budimirovic continues to build up a sampling (FMRP blood draws) effort for a March 2013-present IRB NA_00069920 approved study ‘Genotype-Phenotype: High Resolution FMR1 Genetic and Epigenetic Molecular Assessments in Fragile X Patients.’ The study uses the novel PCR method that precisely quantifies the FMR1 alleles aimed at advancing an understanding of autism in fragile X mutations. The study's preliminary results have been extensively presented nationally and internationally.

A complete list of published work in Dr. Budimirovic's bibliography: http://www.ncbi.nlm.nih.gov/sites/myncbi/1XoOrXgB2c05-/bibliography/48898825/public/?sort=date&di

Related Links

Elsevier Fingerprint Engine Profile for Dejan Budimirovic

Research Publications 

Hinton R, Budimirovic DB, Marschik PB, Talisa VB, Einspieler C, Gipson T, Johnston MV(2013). Parental reports on early language and motor milestones in fragile X syndrome with and without autism spectrum disorders. Dev Neurorehabil. 16(1), 58-66. 

Other Publications

Kaufmann, W.E., Kidd, S.A., Andrews, H.F., Budimirovic, D.B., Esler, A., Haas-Givler, B., Stackhouse, T., Peacock, G., Riley, C., Sherman, S.L., Berry-Kravis, E., Brown, W.T. (2015, in press). Autism spectrum disorder in fragile X syndrome: characterization using the Fragile X Online Registry With Accessible Research Database (FORWARD). Pediatrics. Invited an original article for a Suppl focused on FXS.

Budimirovic, D. B., and Subramanian, M. (2016). Neurobiology of Autism and Intellectual Disability: Fragile X Syndrome. In Johnston, M. V. (Eds.), Neurobiology of Disease (2nd ed.) Chapter 52 (375-384). New York: Oxford University Press.

Budimirovic D.B., and Phan D. Q (2015).  Neurobehavioral Features and Targeted Treatments in     Fragile X Syndrome: Current insights and Future Directions. Engrams 37(4): 5-19. UDK: 616.89-008.434.5-057; doi:10.5937/engrami1504005B; http://scindeks-clanci.ceon.rs/data/pdf/0351-2665/2015/0351-26651504005B.pdf  An invited review.

Budimirovic D.B., Phan D. Q (2016). Challenges in Translating Therapeutic Frontiers in  Clinical Trials: Where Are We Now and What's Next? Madridge J Neuro Sci. 1(1): e1-e3. doi:  10.18689/mjns.2016-e101. An invited editorial.

Budimirovic D., Berry-Kravis E., Erickson C., Hall S., Hessl D., Reiss A., King M., Abbeduto L., Kaufmann W (2016, submitted JNDD-D-16-00077). Updates Report on Tools to Measure Outcomes of Clinical Trials in Fragile X Syndrome. J Neurodev Disord. An invited review. 

Berry-Kravis E., Hagerman R., Visootsak J., Budimirovic D., Kaufmann W., Bear M., Walton-Bowen K., Wang P., Carpenter R (2016, submitted JNDD-D-16-00048). Arbaclofen in Fragile X Syndrome: Results of Phase 3 Trials. J Neurodev Disord. An original invited paper. 

Erickson C., Davenport M., Schaefer T., Wink L., Pedapati E., Sweeney J., Fitzpatrick S., Budimirovic D., Hagerman R., Hessl D., Hagerman R., Brown T., Kaufmann W., Berry-Kravis E. (2016, under submission). Fragile X Targeted Pharmacotherapy: Lessons Learned and Future Directions. J Neurodev Disord.

Selected Poster and Oral Presentations

“Sequential Factor and Cluster Analyzes Support Co-morbid ASD plus Social Anxiety Phenotype in FXS,” (2010) poster at the ADAA Annual Meeting in Baltimore, MD  

“Structural Neuroimaging Correlates of Autism and Social Anxiety in Boys with FXS” (2010) research session on Fragile X and Autism, 12th International Fragile X Conf, Detroit, MI

“Clinical Trials Center at Kennedy Krieger Institute” (2012)poster presentation at the IDDIRC Annual Meeting, Johns Hopkins Hospital, Baltimore, MD

“High Resolution FMR1 Genetic and Epigenetic Molecular Assessments in a Well Characterized Cohort of Full Mutation and Premutation Fragile X Patients” (2013) oral presentation at 1st International Conf on the FMR1 Premutation: Basic Mechanisms and Clinical Involvement, research session “Diagnosis and Screening,” Perugia, Italy

“High Resolution FMR1 Genetic and Epigenetic Molecular Assessments in a Well Characterized Cohort of Full Mutation and PM Fragile X Patients” (2014) poster presentation at ACMG Annual Clinical Genetics Meeting 2014, # 493, Nashville, TN 

“High Resolution FMR1 Genetic and Epigenetic Molecular Assessments in a Well Characterized Cohort of Full Mutation and Premutation Fragile X Patients” (2014) poster presentation at Annual Research Potpourri: Department of Psychiatry and Behavioral Sciences, Johns Hopkins Hospital, Baltimore, MD.

“High Resolution FMR1 Genetic and Epigenetic Molecular Assessments in a Cohort of Full Mutation and Premutation Fragile X Patients” (2014) poster presentation at the 14th International Fragile X Conference, # 15548, P7, Orange County, CA

“Arbaclofen in Fragile X Syndrome: Results of Phase 3 Trials” (2014) oral presentation at the 43rd Annual Meeting of the Child Neurology Society (E. Berry-Kravis, R. Hagerman, J. Visootsak, D. Budimirovic, W. Kaufmann, M. Bear, K. Walton-Bowen, R. Carpenter, P. Wang), Annals of Neurology, Vol 76, Special Issue, suppl 18, pp S174-S174 ( PL1-1), Columbus, OH

“Molecular-clinical profiles in fragile X: High resolution FMR1 genetic and epigenetic molecular assessments in a cohort of full-mutation and premutation patients” (2015) oral poster presentation at the 2nd International Conference on FMR1 Premutation: Basic Mechanisms and Clinical Involvement, Sitges-Barselona, Spain, EU.

“Molecular-clinical profiles in fragile X: High resolution FMR1 genetic and epigenetic molecular assessments in a cohort of full-mutation and premutation patients” by invitation (2016) poster presentation at the Gordon Research Conference "Fragile X and Autism-Related Disorders," West Dover, VT

"A Quantitative FMRP Assay Demonstrates Reliable Performance in Two Different Laboratories and Informs Links between Genotype and Phenotype" (2016)  poster #108 (Eran Bram), 15th International Fragile X Conference, San Antonio, TX    

"Autism Spectrum Disorder in Fragile X Syndrome: Co-Occurring Conditions and Current Treatment," (2016) at oral presentation 183 (Walter Kaufmann), Clinical Science-FORWARD Results, 15th International Fragile X Conference, San Antonio, TX.