Associate Professor, Department of Radiology, Department of Bioengineering and McGowan Institute for Regenerative Medicine University of Pittsburgh Phone: (412) 383-7200 Email: mmm154@pitt.edu

Ph.D., Kings College London

Research Interests

Brain damage and neurodegenerative disease are disabling conditions that affect many millions of patients and their families. Despite a good understanding of the composition of our brains, we still have a rather modest understanding of how these cells produce our day-to-day behavior. Damage to different types of cells or loss of a particular area of brain provide unique insights to the neurobiological basis of behavior. By establishing the fundamental biology of impairments, we can then attempt to re-capitulate this neurological foundation and aim to recover the behavioral dysfunction. To achieve this goal, the key areas of investigation in our laboratory are:

1. To understand the anatomical basis of behavioral impairments

We model neurological conditions, such as stroke, Huntington’s and Parkinson’s disease to mimic the neurological damage and behavioral impairments seen in patients. Using non-invasive neuroimaging and post-mortem histopathological investigations, as well as behavioral test batteries, we then aim to define what aspects of the damage are responsible for the emerging deficits. Using this approach we hope to define particular targets for therapy that could reverse some of these impairments.

2. To replace the brain tissue lost after a stroke

Stroke is characterized by a severe insult to the brain that leads to cellular loss and eventually tissue loss. To replace this lost tissue, we aim to develop tissue engineering strategies that can re-supply new cells to this area that could connect with the rest of the brain. The hope is that eventually this approach could lead to a re-learning of the behaviors that were impaired by tissue loss. The challenges to overcome for this are, nevertheless, considerable and we are but taking the first steps in a long marathon to achieve this.

3. To track in vivo the survival and distribution of transplanted cells by MRI

Cell transplantation and tissue engineering are exciting new avenues to promote recovery from brain damage. However, very little is known about how these cells promote recovery. Being able to visualize the survival and distribution of implanted cells non-invasively and correlate this with behavioral outcomes could be essential to establish exactly how these cells work. We therefore aim to develop non-invasive MRI-based approaches that would allow us to track these cells in vivo.

4. To non-invasively define the cytoarchitectural composition of the brain by MR-histology

Considerable progress has been achieved in describing the cellular composition of the human brain using histopathology, but our knowledge as to the 3 dimensional connections of these cells remains rather limited. Using MRI based techniques at a high resolution, we can nevertheless provide anatomical detail that is not easily derived from histological sections. This MR-histology aims to bridge the analytical gap inbetween in vivo neuroimaging and post-mortem histopathology.

Recent Publications

• Bible, E., Qutachi, O., Chau, D.Y., Alexander, M.R., Shakesheff, K.M., Modo, M. Neo-vascularization of the stroke cavity by implantation of human neural stem cells on VEGF-releasing PLGA microparticles. Biomaterials. In press.
• Vernon, A.C., Natesan, S., Crum, W.R., Cooper, J.D., Modo, M., Williams, S.C.R., Kapur, S. Contrasting effects of haloperidol and lithium on brain structure: An MRI study with post-mortem confirmation. Biological Psychiatry. 2012: 71(10); 855-863. PMID: 22244831.
• Bible, E., Dell’Acqua, F., Solanky, B., Bladucci, A., Crapo, P., Badylak, S.F., Ahrens, E.T., Modo, M. Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodelling in the stroke-damaged rat brain by 19F- and diffusion-MRI. Biomaterials. 2012; 33, 2858-2871. PMID: 22244696.
• Smith, E.J., Stroemer, R.P., Gorenkova, N., Nakajima, M., Crum, W.R., Tang, E., Stevanato, L., Sinden, J.D., Modo, M. Implantation site and lesion topology determine efficacy of a human neural stem cell line in a rat model of stroke. Stem Cells, 30(4), 785-796. PMID: 22213183.
• Patkar, S., Tate, R., Modo, M., Pelvin, R. & Carswell, H.V.O. Conditionally immortalised neural stem cells promote functional recovery and brain plasticity after transient focal cerebral ischaemia in mice. Stem Cell Research. 2012: 8(1); 14-25. PMID:22099017.
• Vernon, AC, Smith, E., Stevanato, L., Modo, M. Selective activation of metabotropic glutamate receptor 7 reduces proliferation and promotes astrocyte differentiation in human ventral mesencephalic neural stem cells. Neurochemistry International. 2011; 59(3): 421-431. PubMed PMID: 21624409.
• Vernon AC, Crum WR, Johansson SM, Modo M. Evolution of extra-nigral damage predicts behavioural deficits in a rat proteasome inhibitor model of Parkinson's disease. PLoS One. 2011 Feb 25;6(2):e17269. PubMed PMID: 21364887.
• Vernon AC, Natesan S, Modo M, Kapur S. Effect of Chronic Antipsychotic Treatment on Brain Structure: A Serial Magnetic Resonance Imaging Study with Ex Vivo and Postmortem Confirmation. Biol Psychiatry. 2011 May 15;69(10):936-44. [Epub 2010 Dec 31] PubMed PMID: 21195390.
• Vernon AC, Johansson SM, Modo MM. Non-invasive evaluation of nigrostriatal neuropathology in a proteasome inhibitor rodent model of Parkinson's disease. BMC Neurosci. 2010 Jan 5;11:1. PubMed PMID: 20051106; PubMed Central PMCID: PMC2824797.
• Ashioti M, Beech JS, Lowe AS, Bernanos M, McCreary A, Modo MM, Williams SC. Neither in vivo MRI nor behavioural assessment indicate therapeutic efficacy for a novel 5HT(1A) agonist in rat models of ischaemic stroke. BMC Neurosci. 2009 Jul 16;10:82. PubMed PMID: 19607699; PubMed Central PMCID: PMC2720976.