Cross Laboratory

Anne Cross, MD

MRI photo left to right
Rob Naismith MD, Anne Cross MD, Victor SongPhD, and Robyn Klein M.D.
Shot for Outlook Magazine

The goal of our research is to understand the mechanisms involved in pathogenesis of inflammation and demyelination in the central nervous system (brain and spinal cord). Our research is primarily focused on the human disease multiple sclerosis (MS), which is very common (1/1000 in the US population). We study human tissues (blood, DNA, RNA, spinal fluid) and perform cutting-edge imaging of the human nervous system. We sometimes employ an animal model for MS known as experimental autoimmune encephalomyelitis (EAE). We are currently performing longitudinal imaging studies to help devise methods to differentiate the various types of pathologies in the human disease, such as demyelination, inflammation with cells and or edema due to blood-brain barrier breakdown, and axon damage and loss. We are funded to devise better methods to measure progression of MS over time, which might be used in clinical trials. We also study the effects of diet and calorie restriction upon neuro-inflammation, having shown previously that calorie restriction ameliorates EAE, the prime animal model for MS, at least partly through the upregulation of adiponectin and downregulation of leptin.

Selected publications:

  1. Lyons JA, San M, Happ MP, and Cross AH: B-cells are critical to induction of experimental allergic encephalomyelitis by protein but not by a short encephalitogenic peptide.Eur. J. Immunol.1999; 29: 3432-3439.
  2. Cross AH, Stark JL, Ramsbottom MJ, Lauber J, Lyons JA: Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. J. Neuroimmunol. 2006; 180:63-70. PMCID: PMC1769354
  3. Stark J, Cross AH: Differential Expression of Suppressors of Cytokine Signaling-1 and -3 and Related Cytokines in Central Nervous System During Remitting versus Non-remitting Forms of Experimental Autoimmune Encephalomyelitis. Int Immunol 2006; 18:347-353.
  4. Cross AH, Ramsbottom MJ, Lyons JA: NOS2 regulates cytokine production and VLA-4 expression in experimental autoimmune encephalomyelitis J Neuroimmunol 2006; 173:79-86.
  5. Naismith RT, Trinkaus K, Cross AH: Phenotype and prognosis in African-Americans with multiple sclerosis: a retrospective chart review. Multiple Sclerosis 2006; 12: 775-781.
  6. Rinker JR II, Trinkaus K, Cross AH: Elevated CSF free kappa light chains correlate with disability prognosis in multiple sclerosis. Neurology 2006; 67:1288-1290.
  7. Lyons JA, Ramsbottom MJ, Mikesell RJ, Cross AH: B cells limit epitope spreading and reduce severity of EAE induced with PLP peptide in BALB/c mice. J Autoimmunity 2008; 31: 149-155. PMCID: PMC2580779
  8. Piccio LM, Stark JL, Cross AH: Chronic Calorie Restriction Attenuates Experimental Autoimmune Encephalomyelitis. J Leuk Biol 2008; 84:940-948. PMCID: PMC2638732
  9. Xu J, Sun S-W, Naismith RT, Snyder AZ, Cross AH, Song SK: Assessing Optic Nerve Pathology with Diffusion MRI: from Mouse to Human. NMR Biomed 2008; 21: 928-40. PMCID: PMC2603138
  10. Naismith RT, Tutlam N, Xu J, Klawiter EC, Shepherd, JB, Song, SK, Cross AH. Optical Coherence Tomography is Less Sensitive than Visual Evoked Potentials in Optic Neuritis Neurology 2009; 73: 46-52. PMCID: PMC2707110
  11. Piccio LM, Buonsanti C, Schmidt RE, Rinker J, Panina-Bordignon P, Cella M, Colonna M, Cross AH: Identification of a novel soluble TREM-2 protein in the cerebrospinal fluid in association with central nervous system inflammation. Brain 2008; 131: 3081-3091 PMCID: PMC2577803
  12. Budde MD, Xie M, Cross AH, Song SK: Axial diffusivity is the primary correlate of axonal injury in the EAE spinal cord: A quantitative pixelwise correlation analysis. J Neuroscience 2009; 29: 2805-2813. PMCID: PMC2673458
  13. Naismith RT, Tutlam NT, Xu J, Klawiter EC, Shepherd JB, Trinkaus K, Song SK, Cross AH. Optical coherence tomography differs in neuromyelitis optica compared with multiple sclerosis. Neurology 2009; 72: 1077-1082 PMCID: PMC2677471
  14. Naismith RT, Piccio L, Lyons JA, Lauber J, Tutlam NT, Parks BJ, Trinkaus K, Song SK, Cross AH: Rituximab add-on therapy for breakthrough relapsing multiple sclerosis: a 52-week phase II trial. Neurology 2010; 74: 1860-1867 PMCID: PMC2882224
  15. Piccio L, Naismith RT, Trinkaus K, Klein RS, Parks BJ, Lyons JA, Cross AH. Changes in B and T lymphocytes and chemokines with rituximab treatment in multiple sclerosis. Arch Neurol 2010; 67: 707-714. PMCID: PMC2918395
  16. Klawiter EC, Piccio L, Lyons JA, Mikesell R, O’Connor KC, Cross AH. Elevated intrathecal myelin oligodendrocyte glycoprotein antibodies in Multiple Sclerosis. Arch Neurol. 2010; 67: 1102-1108. PMCID: PMC3051403
  17. Naismith RT, Xu J, Tutlam N, Scully PT, Trinkaus K, Snyder AZ, Song SS, Cross AH. Increased Diffusivity in Acute Multiple Sclerosis Lesions Predicts Risk of Black Holes. Neurology 2010; 74:1694-701. PMCID2882210
  18. Wang Y, Wang Q, Haldar JP, Yeh FC, Xie M, Sun P, Trinkaus K, Klein RS, Cross AH, Song S-K. Quantification of increased cellularity during inflammatory demyelination. Brain 2011; 134: 3587-9 PMCID: PMC3235568
  19. Klawiter EC, Schmidt RE, Trinkaus K, Liang HF, Budde MD, Naismith RT, Song SK, Cross AH, Benzinger TL. Radial diffusivity predicts demyelination in ex-vivo multiple sclerosis spinal cords. NeuroImage 2011; 55:1454-1460. PMCID: PMC3062747
  20. Naismith RT, Xu J, Tutlam NT, Lancia S, Trinkaus K, Song SK, Cross AH. Diffusion Tensor Imaging in Acute Optic Neuropathies. Predictor of Clinical Outcomes. Arch Neurol 2012; 69: 65-71. PMCID:PMC3489058
  21. Klawiter EC, Xu J, Naismith RT, Benzinger TLS, Shimony JS, Lancia S, Snyder AZ, Trinkaus K, Song SK, Cross AH. Increased radial diffusivity in spinal cord lesions in neuromyelitis optica compared with multiple sclerosis. Mult Scler 2012;18: 1259-68. PMCID: PMC3360125.
  22. Alvarez E, Piccio L, Mikesell RJ, Klawiter EC, Parks BJ, Naismith RT, Cross AH. CXCL13 is a Biomarker of Inflammation in Multiple Sclerosis, Neuromyelitis Optica, and Other Neurological Conditions. Mult Scler. 2013;19:1204-8. PMCID: PMC3959125
  23. Naismith RT, Xu J, Klawiter EC, Lancia S, Tutlam NT, Wagner JM, Qian P, Trinkaus K, Song SK, Cross AH. Spinal cord tract diffusion tensor imaging reveals disability substrate in demyelinating disease. Neurology. 2013; 80:2201-9. PMCID:PMC3721096
  24. Piccio L, Cantoni C, Ramsbottom M, Mikesell B, Cremasco V, Haynes W, Dong LQ, Chan L, Galimberti D, Cross AH. Lack of adiponectin leads to increased lymphocyte activation and worse severity of a mouse model of multiple sclerosis. Eur J Immunol 2013; 43: 2089-2100. PMCID:PMC3901539
  25. Luo J, Yablonskiy DA, Lancia S, Hildebolt C, Cross AH. Gradient echo magnetic resonance imaging correlates with clinical measures and allows visualization of veins within multiple sclerosis lesions. Mult Scler J 2013; 20: 349-355. PMID: 23836876
  26. Wang Y, Sun P, Wang Q, Trinkaus K, Naismith RT, Cross AH, Song SK. Differentiation and quantification of inflammation, demyelination, and axon injury/loss in MS. Brain.2015;138(Pt 5):1223-38. PMCID pending
  27. Longbrake EE, Ramsbottom MJ,Cantoni C,Ghezzi L, Cross AH, Piccio L. Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis. Mult Scler. 2016;22:1061-70. PMCID: PMC4829494
  28. Alvarez EE, Piccio L, Mikesell RJ, Trinkaus K, Parks BJ, Naismith RT, Cross AH. Predicting optimal response to B cell depletion with rituximab in Multiple Sclerosis using CXCL13 index, MRI and clinical measures. Mult Scler J: Exp, Transl Clin 205
  29. Wen J, Yablonskiy D, Luo J, Lancia S, Hildebolt C, Cross AH. Detection and quantification of regional cortical gray matter damage in multiple sclerosis utilizing gradient echo MRI NeuroImage: Clinical 2015; 9:164-175. PMCID: PMC4907986.
  30. Wen J. Yablonskiy DA, Salter A, Cross AH. Limbic system damage in MS: MRI assessment and correlations with clinical testing. PLoS One 2017 Nov 9;12(11):e0187915.
  31. Adusumilli G, Trinkaus K, Sun P, Lancia S, Viox J, Wen J, Naismith RT, Cross AH. Intensity ratio to improve black hole assessment in multiple sclerosis. Mult Scler Rel Dis 2018; 19: 140-147.