Iacovitti Research

Contact

Name: Lorraine Iacovitti, PhD
Position: Professor

233 South 10th Street
320 BLSB
Philadelphia, PA 19107

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Highlighted Publications

Petruk, Svetlana, Jingli Cai, Robyn Sussman, Guizhi Sun, Sina K. Kovermann, Samanta A. Mariani, Bruno Calabretta, Steven B. McMahon, Hugh W. Brock, Lorraine Iacovitti and Alexander Mazo. 2017. “Delayed Accumulation of H3K27me3 on Nascent DNA Is Essential for Recruitment of Transcription Factors at Early Stages of Stem Cell Differentiation.” Molecular Cell 66 (2): 247.

We discovered that during the first hours of induction of differentiation of mammalian embryonic stem cells (ESCs), accumulation of the repressive histone mark H3K27me3 is delayed after DNA replication, indicative of a decondensed chromatin structure in all regions of the replicating genome. This delay provides a critical “window of opportunity” for recruitment of lineage-specific TFs to DNA.

Lin, Ruihe, Jingli Cai, Cody Nathan, Xiaotao Wei, Stephanie Schleidt, Robert Rosenwasser, and Lorraine Iacovitti. 2015. “Neurogenesis Is Enhanced by Stroke in Multiple New Stem Cell Niches along the Ventricular System at Sites of High BBB Permeability.Neurobiology of Disease 74: 229.

We found that both stroke and bFGF induce a dramatic and long-lasting (14 day) rise in the proliferation NSCs capable of differentiating into glial progenitors, astrocyte progenitors and neurons in both the SVZ and CVOs. Additionally, all brain niches were shown to contain a rich vasculature with a blood-brain-barrier (BBB) that is highly permeable to systemically injected sodium fluorescein after stroke.

Bennett, Lori, Ming Yang, Grigori Enikolopov, and Lorraine Iacovitti. 2009. “Circumventricular Organs: A Novel Site of Neural Stem Cells in the Adult Brain.Molecular and Cellular Neuroscience 41 (3): 337.

For the first time, we showed that in adult rat and mouse, the circumventricular organs (CVOs) are rich in neural stem cells which can proliferate and undergo constitutive neurogenesis and gliogenesis, similar to classic stem cell niches (SVZ, SGZ). With the discovery of novel stem cell niches along the entire neuraxis, these pioneering studies have re-written dogma, establishing for the first time the potential for widespread neurogenesis and gliogenesis throughout the adult brain.

Iacovitti, Lorraine, Angela E. Donaldson, Cheryl E. Marshall, Sokreine Suon, and Ming Yang. 2007. “A Protocol for the Differentiation of Human Embryonic Stem Cells into Dopaminergic Neurons Using Only Chemically Defined Human Additives: Studies in Vitro and in Vivo.Brain Research 1127 (1): 19.

We developed a protocol to efficiently differentiate human embryonic stem cell lines into dopaminergic neurons. Furthermore, the transplanted dopaminergic progenitors develop dopaminergic traits 2-3 weeks later in PD rat models.

Kessler, Mark A, Ming Yang, Kandace L Gollomp, Hao Jin, and Lorraine Iacovitti. 2003. “The Human Tyrosine Hydroxylase Gene Promoter.Brain Research. Molecular Brain Research 112 (1–2): 8.

We isolated 13kb of the single copy human tyrosine hydroxylase (hTH) gene and generated an transgenic mouse line using GFP reporter gene driven by this promotor. Our work demonstrated for the first time the ability of a human TH promoter sequence to direct GFP expression to TH+ neurons of the substantia nigra and other TH+ brain regions. These TH reporter mice have been shared with colleagues around the world.

Recent Publications

On the Road from Phenotypic Plasticity to Stem Cell Therapy

A stress-free strategy to correct point mutations in patient iPS cells

Facial grimace testing as an assay of neuropathic pain-related behavior in a mouse model of cervical spinal cord injury

Sphenopalatine ganglion stimulation upregulates transport of temozolomide across the blood-brain barrier

Sphenopalatine ganglion stimulation is a reversible and frequency-dependent modulator of the blood-brain barrier

Subregional differences in astrocytes underlie selective neurodegeneration or protection in Parkinson's disease models in culture

Early Seizure Activity Accelerates Depletion of Hippocampal Neural Stem Cells and Impairs Spatial Discrimination in an Alzheimer's Disease Model

Systemic Factors Trigger Vasculature Cells to Drive Notch Signaling and Neurogenesis in Neural Stem Cells in the Adult Brain

The versatility of RhoA activities in neural differentiation

Differential response in novel stem cell niches of the brain after cervical spinal cord injury and traumatic brain injury

Stepwise impairment of neural stem cell proliferation and neurogenesis concomitant with disruption of blood-brain barrier in recurrent ischemic stroke

Regional microglia are transcriptionally distinct but similarly exacerbate neurodegeneration in a culture model of Parkinson's disease

Robust kinase- and age-dependent dopaminergic and norepinephrine neurodegeneration in LRRK2 G2019S transgenic mice

Delayed Accumulation of H3K27me3 on Nascent DNA Is Essential for Recruitment of Transcription Factors at Early Stages of Stem Cell Differentiation

Structure of Nascent Chromatin Is Essential for Hematopoietic Lineage Specification

Fumarate modulates the immune/inflammatory response and rescues nerve cells and neurological function after stroke in rats

Cell-to-Cell Transmission of Dipeptide Repeat Proteins Linked to C9orf72-ALS/FTD

N-Acetyl cysteine may support dopamine neurons in Parkinson's disease: Preliminary clinical and cell line data

Classic and novel stem cell niches in brain homeostasis and repair

Neuroprotection: Basic mechanisms and translational potential

A stem cell-derived platform for studying single synaptic vesicles in dopaminergic synapses

Stem cell therapy for glaucoma: Science or snake oil?

Neurogenesis is enhanced by stroke in multiple new stem cell niches along the ventricular system at sites of high BBB permeability

The hTH-GFP reporter rat model for the study of Parkinson's disease

Evolutionary conservation of an atypical glucocorticoid-responsive element in the human tyrosine hydroxylase gene