22 S Greene St, Baltimore, MD 21201
Education and Training
2003: M.D., National Taiwan University, Taipei, Taiwan
2008: Ph.D., Pathobiology, Columbia University, New York, NY
2011: Residency, Anatomic Pathology, Johns Hopkins Hospital, Baltimore, MD
2013: Fellowship, Neuropathology, Johns Hopkins Hospital, Baltimore, MD
Dr. Cheng-Ying Ho is an Assistant Professor of Pathology at University of Maryland School of Medicine. Her main research interests are sensory neuroscience and sensory neuropathy. Her laboratory uses a combination of molecular, cellular and genetic approaches to study the impact of the skin microenvironment on the development of sensory neuropathy. Her research is devoted to understanding the role of skin-derived neurotrophic factors in the development and maintenance of the cutaneous mechanosensory nervous system, which is responsible for touch and pain sensation. Neurotrophins and their corresponding receptors are expressed throughout the system, indicating an important role of these molecules in the homeostasis of the system. Impaired skin neurotrophin signaling may underlie the pathogenesis of sensory neuropathy, causing pain and abnormal sensation. The laboratory currently focuses on elucidating the role of skin-derived BDNF for neuroprotection against diabetic neuropathy and for the development of novel therapeutics for diabetic neuropathy.
Dr. Ho publishes extenstively in high-impact journals, including New England Journal of Medicine, Cell, Annals of Neurology and Acta Neuropathologica. She is the recipient of the 2018 Passano Physician Scientist Award and NIH Mentored Clinical Scientist Research Career Development Award (K08).
In addition to sensory neuroscience, she also has research interests in pediatric gliomas and Zika virus-associated neurological complications. She is a leading investigator of a study that provides crucial evidence to support a causal relationship between Zika virus infection and microcephaly.
Cutaneous mechanosensory neurons; touch sensation; peripheral neuropathy; diabetic neuropathy; pediatric low-grade glioma; Zika virus infection
Ho C, Ames HM, Tipton A, Vezina G, Liu JS, Scafidi J, Torii M, Rodriguez FJ, du Plessis A, DeBiasi RL. Differential neuronal susceptibility and apoptosis in congenital ZIKV infection. Ann Neurol 2017; 82: 121-127.
Driggers RW*, Ho C*, Korhonen EM*, Kuivanen S*, Jaaskalainen AJ, Smura T, Rosenberg A, Hill DA, DeBiasi DL, Vezina G, Timofeev J, Rodriguez FJ, Levanov L, Razak J, Iyengar P, Hennenfent A, Kennedy R, Lanciotti R, du Plessis A, Vapalahti O. Zika virus infection with prolonged maternal viremia and fetal brain abnormalities. N Eng J Med 2016; 374: 2142-2151 (* equal contribution).
Ho C, Mobley BC, Gordish-Dressman H, VandenBussche CJ, Mason GE, Bornhorst M, Esbenshade AJ, Tehrani M, Orr BA, LaFrance DR, Devaney JM, Meltzer BW, Hofherr SE, Burger PC, Packer RJ, Rodriguez FJ. A clinicopathologic study of diencephalic pediatric low-grade gliomas with BRAF V600 mutation. Acta Neuropathol 2015; 130:575-585.
Rutlin M*, Ho C*, Abraira VE*, Cassidy C, Woodbury CJ, Ginty DD. The cellular and molecular basis of direction selectivity of Ad-LTMRs. Cell 2014; 159:1640-1651 (* equal contribution).
Ho C, Bar E, Giannini C, Marchionni L, Karajannis MA, Zagzag D, Gutmann DH, Eberhart CG, Rodriguez FJ. MicroRNA profiling in pediatric pilocytic astrocytoma reveals biologically relevant targets including PBX3, NFIB, and METAP2. Neuro Oncol. 2013; 15:69-82.
1. Determine the role of skin-derived BDNF in the maintenance of TrkB-expressing cutaneous sensory receptors. BDNF is known to modulate axon outgrowth and guidance, but its role in axon maintenance remains unclear. Our preliminary data show that skin-specific BDNF knockout mice have a decreased number of Aδ lanceolate endings and Meissner’s corpuscles, both of which express the BDNF receptor TrkB. The findings suggest a positive correlation between skin BDNF level and the number of TrkB-expressing cutaneous sensory receptors. Based on additional observations that skin BDNF levels remain relatively high after completion of cutaneous sensory receptor formation, we hypothesize that skin BDNF is required for the maintenance of TrkB-expressing cutaneous sensory receptors. Using tamoxifen-inducible Keratin 5CreERT2; BDNFflox/flox mice, we will evaluate the effect of skin BDNF depletion on the number and morphology of mature Aδ lanceolate endings and Meissner’s corpuscles.
2. Determine the role of skin-derived BDNF in mediating the neuroprotective effects of Nicotinamide Riboside (NR) and SIRT1 in diabetic neuropathy: We are expanding our research interest in basic sensory neuroscience into mechanisms of neurological diseases. One key investigational area is diabetic neuropathy, the most common complication of diabetes affecting as many as 50% of the patients. Specifically, this research focuses on elucidating the role of skin-derived BDNF in the neuroprotective mechanisms of Nicotinamide Riboside (NR), an essential metabolite and SIRT1, an NAD+-activated protein deacytelase in diabetic neuropathy. Our preliminary findings demonstrate that NR treatment or SIRT1 overexpression reduces and reverses neuropathy in a mouse model of diabetes. A proposed mechanism underlying NR and SIRT1-mediated neuroprotection is to increase BDNF level through deacetylation of MeCP2. Given the expression pattern of SIRT1, we hypothesize that NR and SIRT1 can exert the effect on sensory axons by inducing BDNF expression in skin. To test this hypothesis, we will assess BDNF and MeCP2 acetylation status in skin from diabetic mice treated with NR or overexpressing SIRT1. Furthermore, BDNF will be conditionally deleted in skin of the diabetic mice through Cre-mediated recombination. Intraepidermal nerve fiber density measurements, in vivo whole cell electrophysiological recordings, dynamic touch test and behavioral assays of pain thresholds will be performed to evaluate the effect of skin BDNF deletion on the neuroprotective mechanism of NR and SIRT1. This project is in collaboration with Dr. James Russell of Department of Neurology.
3. Characterize the clinical, pathological and molecular features of pediatric low-grade gliomas: We have a particular interest in pediatric IDH-mutant gliomas and disseminated pilocytic astrocytomas. Using whole-exome and target sequencing, we attempt to identify germline, concurrent driver and secondary mutations in these tumors.
Brain tumors; neuromuscular diseases
Early ultrasounds may not detect microcephaly in mothers with Zika: study
Three ultrasounds done in the early weeks of pregnancy in a Finnish woman living in the United States infected by Zika failed to show signs of brain damage in a fetus later diagnosed with the birth defect microcephaly, U.S. researchers said in a study published on Wednesday.
The woman was not identified but she was infected while traveling on vacation in Mexico, Guatemala and Belize in November 2015. The exact location of transmission was not known.
It was not until the 19th week of her pregnancy that signs of the birth defect first showed up on an ultrasound. A follow up study using magnetic resonance imaging or MRI showed extensive brain abnormalities. Studies showed that the fetal brain had shrunken from a normal head circumference in the 47th percentile during week 16 to the 24th percentile in week 20. Even so, the head circumference was still not small enough to be classified as microcephaly, the researchers reported.
But given the extent of the damages seen on the MRI, the woman elected to terminate the pregnancy in the 21st week.
“What our paper suggests is that physicians should use caution in reassuring patients who have normal fetal ultrasound examinations early in their pregnancies," said Adre du Plessis, Director of the Fetal Medicine Institute at Children’s National Health System in Washington, D.C., a coauthor of the study published on Wednesday in the New England Journal of Medicine.
Du Plessis said single ultrasounds may not capture infection-associated fetal brain abnormalities that may worsen over the course of the pregnancy.
"There is an enormous amount we don't know about this current strain and outbreak of Zika virus. It seems to be behaving differently than in the past," du Plessis said in a conference call with reporters.
"What we do know for sure is if the fetal brain is affected this appears to be a very bad situation," he said.
Zika to date has not been proven to cause microcephaly in babies, but there is growing evidence that suggests a link. The condition is defined by unusually small heads that can result in developmental problems. Brazil - hardest hit by the virus - said it has confirmed more than 900 cases of microcephaly, and considers most of them to be related to Zika infections in the mothers. Brazil is investigating nearly 4,300 additional suspected cases of microcephaly.
In the paper, scientists examined the case of the woman who is from Washington, D.C. She became infected with Zika during her 11th week of pregnancy.
Although Zika infections typically remain present in the blood for 5 to 7 days, the virus in this patient remained present in this woman's blood until 10 days after the fetus was aborted.
Dr. Cheng-Ying Ho, a neuropathologist at Children’s National, said the finding raises questions about whether there is a correlation between the duration of virus infection in the mother and the severity of the brain injuries in the fetus.
An autopsy of the fetus showed high concentrations of the virus in the brain, placenta and umbilical cord. Virus isolated from the brain showed it was still infectious, growing easily in lab dishes of human nerve cells, the study reported.
Study co-author Dr. Roberta DeBiasi, an infectious disease expert at Children’s National, called the high levels of virus in the fetal brain and placenta "concerning and suggests that the virus may be able to hide from the immune system there.
The study authors believe the findings call into question current recommendations for Zika testing in pregnant women, which only recommend testing for presence of the virus within two weeks of an infection. Subsequent tests look for antibodies of the virus but not the virus itself.
Current recommendations do not include the use of MRI imaging tests, which are much more costly than ultrasounds and may not be accessible to pregnant women in countries with Zika transmission.
"What really matters is whether there is evidence of changes in the brain to suggest injury in the context of a proven viral infection in the mother," du Plessis said.
"That is where MRI is the gold standard for picking up changes in the brain, even though it has limitations in terms of availability and cost," du Plessis said.
(Reporting by Julie Steenhuysen; Editing by Bernard Orr)