Ozdinler, P. Hande, PhD



Ozdinler, P. Hande, PhD


Associate Professor



Office Phone

312- 503 2774

Office Fax

312- 503 0872




Ward 10-105 Chicago



Areas of Research

Cell Biology, Molecular Neuroscience, Neurobiology of Disease

Training Grants

Mechanisms of Aging and Demential Training Program (M.A.D)

NU Scholar Profile


Recent Publications on PubMed


Current Research

Current Research

Ozdinler Lab is interested in the cellular and molecular mechanisms that are responsible for selective neuronal vulnerability in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). The main focus is on the corticospinal motor neurons (CSMN), which are modulated by other cortical neurons, and are responsible for the integration and relay of cortical input to spinal targets. CSMN can therefore be considered as the “spokes person of the cerebral cortex” as they have a unique executive function, which makes them the critical cortical component of motor neuron circuitry. Proper function of CSMN allows initiation and control of precise aspects of voluntary movement, and their degeneration contributes to paralysis and loss of motor control in patients. In addition to ALS, Ozdinler Lab is interested in selective neuronal degeneration in other neurodegenerative diseases, such as AD, PD, and investigates unique and common mechanisms for selective neuron loss using neuron-type specific gene expression as a tool.
Ongoing Projects
Common and unique mechanisms between neurodegenerative diseases and cancer
Using evolutionarily refined gene expression as a clue to selective neuronal vulnerability, Ozdinler Lab has investigated the expression pattern of more than 6600 genes and classified them based on their distinct expression patterns in distinct set of neurons that show selective vulnerability in different neurodegenerative diseases. This study revealed common as well as unique networks and pathways that are shared among diseases, and surprisingly brought out the unexpected relationship between cancer and neurodegenerative diseases. The Lab now focuses on the expression profile of select set of genes in post-mortem brain samples in an effort to reveal cellular mechanisms for their degeneration.
Building and developing novel tools to study corticospinal motor neuron biology
One of the limitations in the field is the lack of our ability to visualize motor neurons within the complex and heterogeneous structure of the cerebral cortex. We previously developed approaches to retrogradely label CSMN via direct fluorescent microsphere injection into the corticospinal tract that lies within the dorsal funiculus of the spinal cord. Such approaches require a semi-invasive surgery, and the success of labeling is in part depends on skill and expertise. However, there is a developing need to study the cell biology of vulnerable motor neurons in health and disease. Ozdinler Lab has recently generated a reporter line in which both the corticospinal and spinal motor neurons are genetically labeled by eGFP expression (IP disclosed). Using this novel reporter line, Ozdinler Lab also generated disease models of ALS, in which motor neurons are eGFP labeled. The Lab is now moving forward with the development of novel drug discovery approaches by focusing on the health of the motor neurons both in vitro and in vivo.
Recently Ozdinler Lab identified motor neuron circuitry defects in a novel mouse model, and characterized prominent CSMN degeneration and lack of spinal motor neuron (SMN) function. This is a new mouse model for motor neuron diseases, especially with prominent CSMN input.
Understanding cellular and molecular mechanisms for selective vulnerability
ALS is one of the most complex neurodegenerative diseases. Cellular degeneration can be due tointrinsic and extrinsic factors.
Intrinsic factors could be important for the initiation of selective CSMN degeneration. Ozdinler Lab has taken a systematic approach by using pure populations of callosal projection neurons (CPN; control) and CSMN isolated at early stages of disease progression, and by performing Exon Microarray analysis to reveal the genes that are upregulated/downregulated and that show alternative splice variants. These analyses revealed the molecular signature of vulnerable neurons and indicated the presence of select set of genes, and pathways and networks that could potentially be responsible for selective neuronal vulnerability. The Lab now focuses on the genes and networks that are altered only in diseased neurons as a means to reveal the intrinsic factors that are involved in neuronal degeneration. The results from this work has identified potential early detection markers for ALS and revealed a select set of ion channels that show alternative splicing only in the diseased CSMN as a potential target for drug discovery efforts. Ongoing projects are focusing on validation and confirmation of findings.
Extrinsic factors that are important for the initiation of selective CSMN degeneration, Ozdinler Lab focuses on astrogliosis, microgliosis and the activation of the innate immune response as a potential mechanism. By cross breeding MCP1-CCR2 double transgenic mice generated by Dr. Richard Miller to hSOD1G93A mice, Ozdinler lab has generated MCP1-CCR2-hSOD1G93A triple transgenic mouse model, in which the cells which express MCP1 and CCR2 are genetically labeled by a fluorescent tag. This new mouse model allows not only visualization of the time and extent of immune response in ALS, but also purification of the cells, which initiate the response, using fluorescence activating cell sorting (FACS) mediated approaches. The Lab focuses on the factors that are expressed and secreted by these cells at different stages of disease in both the cortex and the spinal cord. In addition, using these novel tools, the Lab is interested in investigating the potential link between injury to the brain and the rate of ALS initiation and progression especially in veterans and sportsmen.
>Developing new avenues for therapeutic interventions – We believe that in the near future, the molecular basis of neuronal vulnerability will be revealed and candidate targets waiting to be modified will be identified. To be prepared when the moment arises, Ozdinler Lab is developing novel tools that allow cell-type specific genetic modification within CSMN, without affecting other neuron populations in the cerebral cortex, using adeno associated viruses (AAV). Ozdinler Lab has received NUCATS Translational Innovation Award for this work, together with Dr. Martha Bohn. Ongoing efforts are focusing on identification of novel engineered AAV serotypes that have selective tropism for CSMN in the cerebral cortex.

Selected Publications

Selected Publications

Srivastava DP, Woolfrey KM, Jones KA, Anderson CT, Smith KR, Russell TA, Lee H, Yasvoina MV, Wokosin DL, <strong>Ozdinler</strong> PH, Shepherd GM, Penzes P. (2012). An autism-associated variant of epac2 reveals a role for ras/epac2 signaling in controlling basal dendrite maintenance in mice. PLoS Biol. 2012 Jun;10(6):e1001350. Epub 2012 Jun 26.

Jara JH, Villa SR, Khan NA, Bohn MC, <strong>Ozdinler</strong> PH. AAV2 mediated retrograde transduction of corticospinal motor neurons reveals initial and selective apical dendrite degeneration in ALS. Neurobiol Dis. 2012 Aug;47(2):174-83. Epub 2012 Apr 11.

<strong>Ozdinler</strong> PH, Benn S, Yamamoto TH, Güzel M, Brown RH Jr, Macklis JD. Corticospinal motor neurons and related subcerebral projection neurons undergo early and specific neurodegeneration in hSOD1G93A transgenic ALS mice. J Neurosci. 2011 Mar 16;31(11):4166-77.

<strong>Ozdinler</strong> PH, and Macklis JD. (2006) IGF-I specifically enhances axon outgrowth of corticospinal motor neurons. Nature Neuroscience. Nov;9(11):1371-81

Steele AD, Emsley JG, <strong>Ozdinler</strong> PH, Lindquist S, Macklis JD. (2006) Prion protein (PrPc) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis. Proc Natl Acad Sci U S A. 103(9):3416-21

<strong>Ozdinler</strong> PH, Ulupinar E, Erzurumlu RS. (2005) Dose and age-dependent axonal responses of embryonic trigeminal neurons to localized NGF via p75NTR receptor. Journal of Neurobiolgy. 62(2):189-206.

Genç B, <strong>Ozdinler</strong> PH, Mendoza AE, Erzurumlu RS. (2004) A chemoattractant role for NT-3 in proprioceptive axon guidance. PLoS Biol. 2(12)

<strong>Ozdinler</strong> PH, Erzurumlu RS. (2002) Slit2, a branching-arborization factor for sensory axons in the Mammalian CNS. Journal of Neuroscience. 22(11):4540-9.

<strong>Ozdinler</strong> PH, Erzurumlu RS. (2001) Regulation of neurotrophin-induced axonal responses via Rho GTPases. Journal of Comparative Neurology. 438(4):377-87.