Zoology and Physiology

Ram Shukla

Assistant Professor

Zoology and Physiology

Office: Biological Sciences room 314F

email: rshukla@uwyo.edu

About me: I earned my PhD in Biology from the National Institute for Basic Biology, Japan, where my dissertation explored the anatomy of serotonergic infrastructure, including receptors and transporters, across human, macaque, marmoset, and mouse brains. Intrigued about the role of serotonin and other monoaminergic systems in psychiatry, I switched from basic science to translational psychiatric research for my postdoctoral studies at the University of Toronto. This transition expanded my research horizons into behavioral, experimental, and computational domains. My present work focuses on understanding the similarities and differences between psychiatric disorders and their cellular and molecular underpinnings. Something that has intrigued me recently are the ribosomes, and I am dwelling on my hypothesis that these tiny molecular machines, with their mobility around neurons, are responsible for the variable presentation of mood (and other psychiatric) disorders.

Major Research Focus of NeuroPsych Group:

Ribosome Heterogeneity and Mood Disorders: Most stress paradigms downregulate RPGs and upregulate RP pseudogenes These dysregulations may cause stress-induced ribosomal specialization. Downregulated RPGs can change RP stoichiometry, while upregulated RPG pseudogenes can replace RPs with RP paralogs, creating a specialized ribosome. These hypotheses will be tested in postmortem major depression patients, chronic variable stress-exposed mice, and chronically glucocorticoid-stressed primary neurons.

Integrating single-cell transcriptomics and biophysical computer modeling to study stress and recovery: Using our novel single cell transcriptomics-based analytical pipeline, machine learning approaches, and parallels between the stress-related cell-types in the mouse and human, we will test the central hypotheses that the stress and stress recovery states are distinguished by distinct interactions between gut microbial and prefrontal cortex cellular profiles and that the non-pharmacological recovery state closely resembles the direct inverse. The findings will inform a biophysical model of the prefrontal cortex and predict novel therapeutics for reversing stress rather than compensating for it.

 

Selected publications:

1. Zhang X, Eladawi MA, Ryan WG, Fan X, Prevoznik S, Devale T, Ramnani B, Malathi K, Sibille E, Mccullumsmith R, Tomoda T, Shukla R. Ribosomal dysregulation: A conserved pathophysiological mechanism in human depression and mouse chronic stress. (2023) Proceedings of National Academy of Science-Nexus
2. Smail MA, Chandrasena SS, Zhang X, Reddy V, Herman JP, Sherif M and Shukla R. Differential vulnerability of Anterior cingulate cortex cell-types to disease and drugs. (2022) Molecular Psychiatry
3. Alnafisah RS, Reigle J, O’Donovan S, Funk AJ, Meller J, Mccullumsmith R and Shukla R. Pharmacological impacts on schizophrenia functional analysis: a postmortem proteome study. (2022) Neuropsychopharmacology
4. Reddy V, Sherif M, and Shukla R. Integrating single-cell transcriptomics and microcircuit computer modelling. (2021) Current Opinion in Pharmacology

5. Smail MA, Wu X, Henkel ND, Eby HM, Herman JP, Mccullumsmith RE, and Shukla R. Similarities and dissimilarities between psychiatric cluster disorders. (2021) Molecular Psychiatry
6. O’Donovan S, Mccullumsmith R and Shukla R. Neurosciences: Advances in the field. (2022) Current Opinion in Pharmacology (Editorial)
7. Wu X, Shukla R*, Alganem K, Depasquale E, Reigle J, Meller J, Mccullumsmith R. Transcriptional profile of pyramidal neurons in chronic schizophrenia reveals lamina-specific dysfunction of neuronal immunity. (2021). Molecular Psychiatry *Equal contribution
8. Henkel ND, Smail MA, Wu X, Enright HA, Fisher N, Eby HM, Mccullumsmith R and Shukla R. Cellular, molecular, and therapeutic characterization of pilocarpine-induced temporal lobe epilepsy. (2021) Scientific Report
9. Shukla R*, Newton D, Sumitomo A, Zare H, Mccullumsmith R, Lewis D, Tomoda T, and Sibille E. Molecular Characterization of Depression Trait and State. (2021) Molecular Psychiatry. *Corresponding
10. Shukla R*, Henkel N, Alganem K, Hamoud A, Reigle J, Alnafisah RS, et al. Signature based approaches for Informed Drug Repurposing: Targeting CNS Disorders. (2020) Invited review. *Corresponding
11. Shukla R, Oh H, Sibille E. Molecular and cellular evidence for age by disease interactions: updates and path forward. (2019) American Journal of Geriatric Psychiatry.
12. Shukla R, Prevot TD, French L, Isserlin R, Rocco BR, Banasr M, and Sibille E. The relative contributions of cell-dependent cortical microcircuit aging to cognition and anxiety. (2019) Biological Psychiatry.
13. Shukla R, Watakabe A, and Yamamori T. mRNA expression profile of serotonin receptor subtypes and distribution of serotonergic terminations in marmoset brain. (2014) Frontiers Neural Circuits.