Andrew Dhawan Laboratory

Research

Overview

Neurogenetic and neuro-oncologic conditions remain poorly understood, are individually rare and are clinically heterogeneous. Our lab’s mission is to advance care for neurological diseases and neurogenetic disorders using experimental biology, computational genomics, and mathematical modeling. Our multi-faceted approach to these diseases, we hope, will reveal reliable, readily implementable, mechanistic biomarkers for clinical translation. Our overarching vision is to extend patient quality and quantity of life, with evidence-based interventions in neurologic disease. 

Neurogenetic and neuro-oncologic conditions remain poorly understood, are individually rare, and are clinically heterogeneous. Our lab’s mission is to advance care for neurological diseases and neurogenetic disorders using experimental biology, computational genomics, and mathematical modeling. Our multi-faceted approach to these diseases, we hope, will reveal reliable, readily implementable, mechanistic biomarkers for clinical translation. Our overarching vision is to extend patient quality and quantity of life, with evidence-based interventions in neurologic disease.

Gene signatures and non-coding RNA

The genomic revolution has provided incredibly detailed mechanistic insights into how individual cells behave in cancers, and how these patterns of activity drive disease. Understanding these large genomic datasets has relied on gene signatures, patterns of gene expression that indicate a phenotype of interest. Gene signatures have been developed for myriad biological phenomena: prognosis, cellular state, and diagnosis. However, most published gene signatures have not shown biological or clinical relevance outside the original datasets from which they were derived. We seek to identify new gene signatures, and new methods of developing gene signatures, with clinical relevance to bring these powerful tools to the clinic to help physicians more effectively prognosticate and treat disease. Specifically, we are interested in how non-coding RNA expression may function as a biomarker for neurological disorders. miRNA and circular RNA (circRNA) signatures may be detected readily in various biofluids and may help diagnose neurologic diseases earlier than alternative methods. We seek to identify specific miRNA and circRNA signatures that can function as potential diagnostic and therapeutic markers, using cerebrospinal fluid, blood, and tissue assays.

SigQC is an R package for the quality control assessment of gene signatures.

Disease risk assessment and prediction

We have broad collaborations with the goal of developing  risk models for complications and disease progression. By combining genomic profiling, imaging, and clinical data, we can identify predictors for specific outcomes or disease subtypes. We also seek to use wearable devices in patient care to better understand how disease impacts function, and whether continuous remote monitoring, in diseases like glioblastoma, can improve outcomes and care.

Clinical care for rare neurologic disorders

A further focus of our lab is the care for individuals with rare neurologic disorders. Dr. Dhawan has been involved in the care for individuals with PTEN hamartoma tumor syndrome, a rare genetic disorder leading to a predisposition towards tumors and neurodevelopmental challenges. The expanding spectrum of neurologic challenges faced by individuals with PTEN hamartoma tumor syndrome is a strong interest of the lab, and we have helped lead the development of clinical care guidelines for the management of neurologic features of this condition.

Climate change and neurologic disease

Our lab has been among the first to comprehensively characterize the associations between climate and neurologic health. As a leader in this space, and as the climate changes, we seek to frame priorities for future adaptation of neurologic care, improve study methodology to better understand climate and neurologic health, and understand biological mechanisms of how neurologic health and climate are interrelated. 

Selected Publications

Dhawan Andrew, Eng Charis. Is the gene mutation associated with thrombosis? Cleve Clin J Med. 2023. 37914198.

Scarborough Jessica A, Dhawan Andrew, Scott Jacob G. Exploiting convergent phenotypes to derive a pan-cancer cisplatin response gene expression signature. NPJ Precis Oncol. 2023. 37076665.

Dhawan Andrew, Yeaney Gabrielle, Lathia Justin D. EGFR Pathway Expression Persists in Recurrent Glioblastoma Independent of Amplification Status. Cancers (Basel). 2023. 36765632.

Ahluwalia Manmeet S, Peereboom David M, Dhawan Andrew. Phase IIa Study of SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma. J Clin Oncol. 2023. 36521103.

Louis Shreya, Carlson Alise K, Suresh Abhilash, Rim Joshua, Mays MaryAnn, Ontaneda Daniel, Dhawan Andrew. Impacts of Climate Change and Air Pollution on Neurologic Health, Disease, and Practice: A Scoping Review. Neurology. 2023. 36384657.

Dhawan Andrew. Machine Learning Using Gene-Sets to Infer miRNA Function. Adv Exp Med Biol. 2022. 36352216.

Dhawan Andrew, Peereboom David M, Stevens Glen Hj. First clinical experience with belzutifan in von Hippel-Lindau disease associated CNS hemangioblastoma. CNS Oncol. 2022. 35819008.

Weaver Davis T, Scarborough Jessica, Dhawan Andrew, Scott Jacob G. Network potential identifies therapeutic miRNA cocktails in Ewing sarcoma. PLoS Comput Biol. 2021. 34662337.

Dhawan Andrew. Extracellular miRNA biomarkers in neurologic disease: is cerebrospinal fluid helpful? Biomark Med. 2021. 34514843.

Weaver Davis T, Gopalakrishnan Vishhvaan, Card Kyle J, Crozier Dena, Dhawan Andrew, Dinh Mina N, Dolson Emily, Farrokhian Nathan, Hitomi Masahiro, Ho Emily, King Eshan S, Cadnum Jennifer L, Donskey Curtis J, Krishnan Nikhil, Kuzmin Gleb, Pelesko Julia, Scarborough Jessica A, Sedor Geoff, Scott Jacob G. UV decontamination of personal protective equipment with idle laboratory biosafety cabinets during the COVID-19 pandemic. PLoS One. 2021. 34310599.

Dhawan Andrew. Mathematical Modeling of ceRNA-Based Interactions. Methods Mol Biol. 2021. 34165711.

Louis Shreya, Dhawan Andrew, Newey Christopher, Nair Dileep, Jehi Lara, Hantus Stephen, Punia Vineet. Continuous electroencephalography characteristics and acute symptomatic seizures in COVID-19 patients. Clin Neurophysiol. 2020. 32949985.

Scarborough Jessica A, McClure Erin, Anderson Peter, Dhawan Andrew, Durmaz Arda, Hitomi Masahiro, Scott Jacob G. Identifying States of Collateral Sensitivity during the Evolution of Therapeutic Resistance in Ewing's Sarcoma. iScience. 2020. 32623338.

Scott Jacob. Role of gene signatures combined with pathology in classification of oropharynx head and neck cancer. Sci Rep. 2020. 32576885.

Yoon Nara, Durmaz Arda, Dhawan Andrew, Abazeed Mohamed, Mian Omar, Scott Jacob. Resistance to targeted therapies as a multifactorial, gradual adaptation to inhibitor specific selective pressures. Nat Commun. 2020. 32409712.

Dhawan Andrew, Scott Jacob G. Mathematical oncology and it's application in non melanoma skin cancer - A primer for radiation oncology professionals. Oral Oncol. 2020. 32109841.

Dhawan Andrew. A computationally inspired in-vivo approach identifies a link between amygdalar transcriptional heterogeneity, socialization and anxiety. Transl Psychiatry. 2019. 31819040.

Dhawan Andrew. : a database of oxic and hypoxic radiation response gene signatures and their utility in pre-clinical research. Br J Radiol. 2019. 31538514.

Dhawan Andrew. Cooperative adaptation to therapy (CAT) confers resistance in heterogeneous non-small cell lung cancer. PLoS Comput Biol. 2019. 31449515.

Scott Jacob G. Guidelines for using sigQC for systematic evaluation of gene signatures. Nat Protoc. 2019. 30971781.