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research interests

research interests


My scientific vision is to cut across intellectual silos and integrate multiple streams of data to answer big questions in Alzheimer’s disease (AD) research. My research focus is to determine how aspects of brain connectivity could be developed as biomarkers of progression in AD. My current project is to derive patient-specific measures of resting-state functional connectivity based on individual cortical and tract anatomy.

My PhD thesis was focused on the interaction of neurovascular and neuronal damage in mouse models of AD. To date, increased amyloid-beta peptide, a cleavage product of the amyloid precursor protein (APP), has been advocated as the common mediator of both the neuronal and vascular damage incurred in AD. Recently, the thiazolidinedione pioglitazone was demonstrated to counter several pathological processes in the brains of aged amyloid-beta-overproducing APP transgenic mice. My PhD work showed that pioglitazone treatment commencing in young APP mice fully reversed cerebrovascular dysfunction and partially reversed cognitive impairment. However, pioglitazone failed to improve the attenuated cognitive task-induced neuroanatomical plasticity in the hippocampus that we reported for the first time in AD mice using magnetic resonance imaging methods. The vascular pathology appears to occur early in the disease process relative to amyloid-beta peptide deposition and cognitive deficits. Thus it is important to understand the molecular mechanisms of amyloid-beta-induced vascular pathology in AD and its reversal by candidate therapies, such as pioglitazone. To this end, I developed a new technique for the extraction of vascular protein from the mouse brain, compatible with two complementary mass spectrometry methods, to characterize the cerebrovascular proteome of normal (wild-type) mice. This approach allowed the identification of 6,630 proteins, mainly distributed in the endothelial and muscular compartments of the vascular wall. We found a few hundred proteins with significantly altered levels (upregulated or downregulated) in cerebral vessels of amyloid-beta-overproducing APP mice, including proteins related to vessel structure, vasomotricity and free radical production. Pioglitazone treatment exerted significant benefits in the APP mice, with over a third of the altered protein levels returned to wild-type levels. These results suggest that pioglitazone may be of benefit to AD patients with concurrent cerebrovascular deficits. In addition, some of the identified proteins could represent potential biomarkers for assessing the efficacy of therapies targeting cerebrovascular deficits in AD.

My MSc work was performed in the context of the Vervet Functional Genome Project, the goal of which was to (1) develop a well-characterized primate model for the study of primate genome rearrangements and evolution and (2) to improve the understanding of complex processes such as neuro-development and degeneration. Within the scope of this overall project, my focus was to study genome reorganization in the vervet monkey using both bioinformatics tools and laboratory protocols. Prior to my MSc, I worked at the Montreal Neurological Institute studying epilepsy genetics.

To summarize, my scientific approach is to integrate observations from in-vivo imaging with genomics, proteomics and bioinformatics in the study of AD and other neurodegenerative diseases, with the goal of discovering new therapeutic targets and improving methods to speed the drug discovery process.


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Peer-Reviewed Papers


In Review

  1. Badhwar A, Collin-Verreault Y, Orban P, Chouinard I, Vogel J, Duchesne S, Bellec P. Consistency values of resting-state fMRI connectivity maps from a single individual over 3.5 years, 13 sites and 3 vendors using the Canadian Dementia Imaging Protocol. (Data In Brief, currently under revision following a positive first review)
  2. Bielczyk N, Ando A*, Badhwar A*, Caldinelli C*, Gao M*, Haugg A*, Hernandez L*, Ito K*, Kessler D*, Lurie D*, Makary MM*, Nikolaidis A*, Veldsman M*, OHBM Student and Postdoc Special Interest Group. Effective self-management for early career researchers in the natural sciences.
    * denotes equal contribution with ordering of names in alphabetical order. DOI 10.17605/OSF.IO/W6EMK
  3. Dansereau C, Tam A, Badhwar A, Urchs S, Orban P, Rosa-Neto P, Bellec P. Identification of a brain signature highly predictive of future progression to Alzheimer’s dementia. (in review) preprint available at doi: https://arXiv:1712.08058
  4. Orban P, Tam A, Urchs S, Savard M, Madjar C, Badhwar A, Dansereau C, Vogel J, Schmuel A, Dagher A, Villeneuve S, Poirier J, Rosa Neto P, Breitner J, Bellec P. Subtypes of functional brain connectivity as early markers of neurodegeneration in Alzheimer's disease. (in review); preprint available at doi: https://doi.org/10.1101/195164
  5. Benhajali Y, Badhwar A, Spiers H, Urchs S, Armoza J, Ong T, Pérusse D, Bellec P. A standardized protocol for efficient and reliable quality control of brain registration in functional MRI studies. Preprint available at https://doi.org/10.31234/osf.io/m9us6

Published

  1. Badhwar A, Haqqani A. Biomarker potential of brain-secreted extracellular vesicles in blood in Alzheimer’s disease. Alzheimers Dement 2019 (in press)
  2. Badhwar A, McFall GP, Sapkota S, Black SE, Chertkow H, Duchesne S, Masellis M, Li L, Dixon RA, Bellec P. A multiomics approach to heterogeneity in Alzheimer's disease: focused review and roadmap. Brain, pii: awz384 (doi: doi.org/10.1093/brain/awz384) 2019.
  3. Badhwar A, Collin-Verreault Y, Orban P, Chouinard I, Vogel J, Duchesne S, Bellec P. Multivariate consistency of resting-state fMRI connectivity maps acquired on a single individual over 2.5 years, 13 sites and 3 vendors. NeuroImage 205:116210, (doi: 10.1016/j.neuroimage.2019.116210) 2019.
  4. Cuperlovic-Culf M, Badhwar A. Recent advances from metabolomics and lipidomics application in Alzheimer’s disease inspiring drug discovery. Expert Opinion on Drug Discovery 16:1-13, (doi: 10.1080/17460441.2020.1674808) 2019.
  5. Duchesne S, Dieumegarde L, Chouinard I, Farokhian F, Badhwar A, Bellec P, Tétreault P, Descoteaux M, Beaulieu C, Potvin O, and the CIMA-Q group* and the CCNA group. Structural and functional multi-platform magnetic resonance imaging series of a single human volunteer over 15+ years. Scientific Data 6, Article number: 6(1):245 (doi: 10.1038/s41597-019-0262-8), 2019.
  6. Sappey-Marinier D, Suprano I, Delon-Martin C, Kocevar G, Stamile C, Hannoun S, Achard S, Badhwar A, Fourneret P, Revol O, Nusbaum F. Topological reorganization of brain networks in children with high intelligence quotient: a resting state fMRI study. Frontiers in Human Neuroscience 13:241 (doi: 10.3389/fnhum.2019.00241), 2019.
  7. Bielczyk N, Veldsman M, Ando A, Caldinelli C, Makary MM, Nikolaidis A, Scelsi MA, Stefan M, OHBM Student and Postdoc Special Interest Group, Badhwar A. Mentoring early career researchers: Lessons from the Organization for Human Brain Mapping International Mentoring Programme. European Journal of Neuroscience 49(9):1069-1076 (doi: 10.1111/ejn.14320), 2018.
  8. Badhwar A, Tam A, Dansereau C, Orban P, Toro R, Hoffstaedter F, Bellec P. Resting-state network dysfunction in Alzheimer’s disease: a systematic review and meta-analysis. Alzheimers Dement 18(8):73-85, 2017.
  9. Lajoie I, Nugent S, Debacker C, Dyson K, Tancredi FB, Badhwar A, Belleville S, Deschaintre Y, Bellec P, Doyon J, Bocti C, Gauthier S, Arnold D, Kergoat MJ, Chertkow H, Monchi O, Hoge RD. Application of calibrated fMRI in Alzheimer’s disease. Neuroimage:Clinical 15:348-358, 2017.
  10. Tam A, Dansereau C, Badhwar A, Orban P, Belleville S, Chertkow H, Dagher A, Hanganu A, Monchi O, Rosa-Neto P, Shmuel A, Breitner J, Bellec P. A dataset of multiresolution functional brain parcellation in an elderly population with no or mild cognitive impairment. Data in Brief 9:1122-1129, 2016.
  11. Badhwar A. Kennedy D, Poline JP, Toro R. Distributed collaboration: the case for the enhancement of Brainspell's interface. GigaScience (doi: http://dx.doi.org/10.5524/100216), 2016.
  12. Badhwar A, Brown R, Stamimirovic D, Haqqani A, Hamel E. Proteomic differences in brain vessels of Alzheimer’s disease mice: normalization by PPARγ agonist pioglitazone. J Cereb Blood Flow Metab. 2016 Jun 23. pii: 0271678X16655172. [Epub ahead of print]
  13. Tam A, Dansereau C, Badhwar A, Orban P, Belleville S, Chertkow H, Dagher A, Hanganu A, Monchi O, Rosa-Neto P, Shmuel A, Wang S, Breitner J, Bellec P. Alzheimer’s Disease Neuroimaging Initiative. Common Effects of Amnestic Mild Cognitive Impairment on Resting-State Connectivity Across Four Independent Studies. Front Aging Neurosci. 24;7:242. doi: 10.3389/fnagi.2015.00242. eCollection 2015.
  14. Hoge R.D, Badhwar A, Doyon J, Ostry D. Improving Sensitivity and Specificity in BOLD fMRI Using Simultaneous Multi-Slice Acquisition. MAGNETOM Flash, 2015.
  15. Badhwar A, Stanimirovic DB, Hamel E, Haqqani AS. The Proteome of mouse cerebral arteries. J Cereb Blood Flow Metab. 34:1033-1046 2014 Mar 26.
  16. Badhwar A, Lerch JP, Hamel E, Sled JG. Impaired structural correlates of memory in Alzheimer’s disease mice. Neuroimage Clinical 3:290-300, 2013.
  17. Jansen A*, Sancak O*, D’Agostino MD*, Badhwar A, Roberts P, Gobbi G, Wilkinson R, Melanson D, Tampieri D, Koenekoop R, Gans M, Maat-Kievit A, Goedbloed M3, van den Ouweland AMW, Nellist M, Pandolfo M, McQueen M, Sims K, Thiele E, Dubeau F, Andermann F, Kwiatkowski DJ, Halley DJJ, Andermann E. Unusually mild tuberous sclerosis phenotype is associated with TSC2 R905Q mutation. Ann Neurol. 60(5):528-39, 2006. (* denotes equal contribution)
  18. Al-Asmi A, Jansen A*, Badhwar A*, Dubeau F, Tampieri D, Shustik C, Mercho S, Savard G, Dobson-Stone C, Monaco A, Andermann F, Andermann E. Familial temporal lobe epilepsy as a presenting feature of chorea-acanthocytosis. Epilepsia 46(8):1256-63, 2005. (* denotes equal contribution)
  19. Badhwar A, Jansen A, Andermann F, Pandolfo A, Andermann E. Striking intrafamilial phenotypic variability and spastic paraplegia in the presence of similar homozygous expansions of the FRDA1 gene. Mov Disord. 19(12):1424-31, 2004.
  20. Badhwar A, Berkovic SF, Dowling JP, Gonzales M, Narayanan S, Brodtmann A, Berzen L, Caviness J, Trenkwalder C, Winkelmann J, Rivest J, Lambert M, Hernandez-Cossio O, Carpenter S, Andermann F, Andermann E. Action myoclonus-renal failure syndrome: characterization of a unique cerebro-renal disorder. Brain 127(10):2173-82, 2004.
  21. Badhwar A, Siren A, Andermann E, Andermann F. Myoclonic status epilepticus: video presentation. Mov Disord. 17(2):409-11, 2002.
  22. Siegel AM, Andermann F, Badhwar A, Rouleau GA, Dam M, Hopf HC, Dichgans J, Sturzenegger M, Hopf NJ, Yasui N, Stepper F, Killer M, Vanneste JA, Acciarri N, Drigo P, Christensen J, Braun V, Konu D, Andermann E. Anticipation in familial cavernous angioma: ascertainment bias or genetic cause. Acta Neurol Scand. 98(6):372-6, 1998.
  23. Siegel AM, Andermann E, Badhwar A, Rouleau GA, Wolford GL, Andermann F, Hess. Anticipation in familial cavernous angioma: a study of 52 families from International Familial Cavernous Angioma Study. IFCAS Group. Lancet 352(9141):1676-7, 1998.

Published Abstracts (2010 -)

  1. Surendra A, Loudjani S, Cuperlovic-Culf M, Badhwar A. ADMetaboMine Database - published measurements of metabolites in brain and body fluids in Alzheimer’s disease. Annual meeting of the Organization for Human Brain Mapping, Montreal, Canada, 2020 (submitted).
  2. Benhajali Y, Badhwar A, Spiers H, Urchs S, Armoza J, Ong T, Pérusse D, Bellec P. A standardized protocol for reliable quality control of brain registration in function MRI studies. Annual meeting of the Organization for Human Brain Mapping, Montreal, Canada, 2020 (submitted).
  3. Duchesne S, Potvin O, and CDIP Group* The Canadian Dementia Imaging Protocol is effective at reducing variability in multi-centric longitudinal studies. *denotes that I am part of the CDIP group. Annual meeting of the International Society for Magnetic Resonance in Medicine, Sydney, Australia, 2020 (submitted). *denotes that I am a member of the CDIP group.
  4. Badhwar A, Bore A, Sharmarke H, Rastegarnia S, Chakravarty M, Kazazian C, Devenyi G.A, Duchesne S, Evans A, Descoteaux M, Beaulieu C, Bellec P. CCNA standardized MRI biomarkers: Initial quality assessment. Canadian Consortium on Neurodegeneration in Aging (CCNA) Science Day and Partners Forum 2019, Quebec City
  5. Badhwar A, Haqqani A. Biomarker potential of brain-secreted extracellular vesicles in blood in Alzheimer’s disease. Canadian Consortium on Neurodegeneration in Aging (CCNA) Science Day and Partners Forum 2019, Quebec City
  6. Badhwar A, McFall GP, Sapkota S, Chertkow H, Dixon RA, Bellec P. Toward discovery of multiomics biotypes of Alzheimer’s disease: A focused review and proposed roadmap. Annual meeting of the Organization for Human Brain Mapping, Rome, Italy, 2019.
  7. Benhajali Y, Vainik U, Moreau C, Badhwar A, Surchs S, Perusse D, Bellec P. Two highly pleiotropic clusters of brain activation in the Human Connectome Project. Annual meeting of the Organization for Human Brain Mapping, Rome, Italy, 2019.
  8. Badhwar A, Collin-Verreault Y, Orban P, Urchs S, Chouinard I, Vogel J, Potvin O, Duchesne S, Bellec P. Consistency of resting-state fMRI connectivity on a single individual over 2.5 years and 13 sites using the Canadian dementia imaging protocol. INCF Neuorinformatics Conference, Montreal, Canada, 2018.
  9. Benhajali Y, Badhwar A, Surchs S, Bellec P. Crowd sourced quality control of brain registration on the Zooniverse platform. INCF Neuorinformatics Conference, Montreal, Canada, 2018.
  10. Badhwar A, Collin-Verreault Y, Orban P, Urchs S, Chouinard I, Vogel J, Safi-Harab M, Duchesne S, Bellec P. The Canadian Dementia Imaging Protocol: consistency of resting-state fMRI connectivity in a traveling human phantom. Annual meeting of the Organization for Human Brain Mapping, Singapore, Singapore, 2018.
  11. Badhwar A, McFall GP, Sapkota S, Chertkow H, Dixon RA, Bellec P. Toward discovery of multi-omics biotypes of Alzheimer’s disease: A focused review and proposed roadmap. Alzheimer's Association International Conference, London, England, 2017.
  12. Dansereau C, Tam A, Badhwar A, Urchs S, Orban P, Rosa-Neto P, Bellec P, Alzheimer’s Disease Neuroimaging Initiative. Multimodal identification of a brain biotype highly predictive of future progression to Alzheimer’s dementia. Alzheimer's Association International Conference, London, England, 2017.
  13. Badhwar A, Quirion PO, Benhajali Y, Glatard T, Dansereau C, Orban P, Duchesne S, Evans A, Dixon R, Bellec P. A reproducible, standardized workflow for the generation of fMRI markers of neurodegeneration. Annual meeting of the Organization for Human Brain Mapping, Vancouver, Canada, 2017.
  14. Badhwar A, Chen J, Dansereau C, Devernyi GA, Iturria Medina Y, Orban P, Quirion PO, Beaulieu C, Chakravarty M, Descoteaux M, Duchesne S, Evans A, Dixon R, Bellec P. The COMPASS-ND processed MRI project: a multimodal collection of standardized and sensitive markers to study neurodegeneration. Canadian Consortium on Neurodegeneration in Aging (CCNA) Annual Meeting, Vancouver, Canada, 2016.
  15. Badhwar A, Sidhu J, Bellec P, Descoteaux M, Petrides M. In vivo anatomy of the temporo-frontal extreme capsule fasciculus. Annual Meeting of the Organization for Human Brain Mapping Conference, Geneva, Switzerland, 2016.
  16. Badhwar A, Brown R, Delaney C, Stanimirovic D, Haqqani A, Hamel E. Altered cerebrovascular proteome in Alzheimer’s disease mice and the effect of pharmacotherapy. International Conference on Promoting Healthy Brain Aging and Preventing Dementia, Banff, Alberta, 2016.
  17. Badhwar A. Tam A, Dansereau C, Orban P, Bellec P. Meta-analysis of resting-state connectivity differences between normal aging and Alzheimer's disease. International Conference on Promoting Healthy Brain Aging and Preventing Dementia, Banff, Alberta, 2016.
  18. Orban P, Chouinard I, A. Badhwar A, Duchesne S, Bellec P. Reproducibility of resting-state fMRI connectivity maps across sessions and sites in a single individual. International Conference on Promoting Healthy Brain Aging and Preventing Dementia, Banff, Alberta, 2016.
  19. Badhwar A, Albouy G, Doyon J, Hoge R, Tannenbaum C. Reproducibility of fMRI activations associated with bladder filling: Implications for trial designs. Annual Meeting of the Organization for Human Brain Mapping Conference, Honolulu, USA, 2015.
  20. Badhwar A, Stanimirovic D, Haqqani A, Hamel E. Quantitative proteomics of Alzheimer’s disease-like cerebral vasculature in TGF-ß1 overexpressing mice and its perturbation by pioglitazone. Alzheimer's Association International Conference, Vancouver, Canada, 2012. Alzheimer's & Dementia 8(Supplement 4):650, 2012.
  21. Badhwar A, Brown R, Delaney C, Stanimirovic D, Haqqani A, Hamel E. Rescue of amyloid-beta induced alterations in cerebrovascular protein expression by pioglitazone in APP mice: link to functional recovery in the cerebrovasculature. Alzheimer's Association International Conference, Vancouver, Canada, 2012. Alzheimer's & Dementia 8(Supplement 4):574-575, 2012.
  22. Badhwar A, Lerch JP, Sled JG, Hamel E. Early treatment with pioglitazone in APP transgenic mice shows focal hippocampal volume increase related to improved cognitive performance. International Conference on Alzheimer's Disease, Honolulu, USA, 2010. Alzheimer's & Dementia 6(4, Supplement):e7, 2010.





 

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