Pembe Hande Ozdinler Intl Innovation Women in Science Research Media mh indd

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Could you begin by explaining what 

amyotrophic lateral sclerosis (ALS) is and how 

it affects motor neurons in the spinal cord?

ALS is one of the most complex 

neurodegenerative diseases, where the motor 

neurons in the spinal cord, brainstem and 

the brain deteriorate. Because it is the motor 

neurons that are primarily affected, the patient 

cannot move, but can remember and still have 

cognitive function. The neurons in the brain and 

spinal cord that are important for movement 

die, which results in paralysis and, eventually, 

death. However, other neurons remain relatively 

healthy in the patient.

Why did you become interested in studying 

ALS? What made it particularly important for 

you to focus your research on corticospinal 

motor neurons (CSMN)?

The reason has a personal touch behind it. I lost 

my brother to a thalamic stroke at the age of 23 

and, at the time, knew nothing about the brain. I 

changed my topic and programme, and earned 

a PhD in the fields of cell biology, anatomy and 

neuroscience at Louisiana State University 

Health Sciences Center. After that, I went to 

the Harvard Medical School Neurosurgery 

Department for postdoctoral studies.

I focused on corticospinal motor neurons 

during my studies and these are the neurons 

that die in ALS patients’ brains. I immediately 

developed a personal bond with the patients, 

their caregivers and loved ones.

You were the first person to label, isolate and 

culture CSMN. What did you discover about 

these upper motor neurons’ requirements for 

survival and growth?

We found many cellular pathways and events 

that are crucial for the function and health 

of CSMN. When these cellular events are 

perturbed, or become dysfunctional, CSMN 

begin to show signs of vulnerability and early 

degeneration. One example is the endoplasmic 

reticulum (ER) stress; when there is increased 

ER stress, other neurons manage to cope with 

it, but CSMN cannot do so as effectively as 

other neurons.

Your team received a Northwestern University 

Translational Innovation Award for creating 

an effective method for selectively targeting 

CSMN without affecting other neuron 

populations. How does this retrograde 

transduction approach work?

Transducing just the neurons of interest is 

extremely important for developing long-term 

and effective treatment strategies. The cerebral 

cortex is complex, with billions of neurons 

that are different in type, function, size and 

shape, and all interconnected with each other. 

However, in diseases, not all neurons show 

initial vulnerability; for reasons still unknown, 

only a select set of neuron populations 

show primary vulnerability and undergo 

degeneration. When we better understand the 

causes that underlie these diseases, we will 

want to deliver the therapies directly to these 

neurons, without affecting other neurons in the 

brain so that we do not perturb their balance.

How did you come to generate and 

characterise a reporter line that made upper 

motor neurons visible in the brain?

We searched thousands of genes that 

showed high levels of expression in CSMN 

and are longlasting and stable. UCHL1 gene 

is expressed in almost all neurons to varying 

degrees, but CSMN express high levels, with 

expression present even at very old ages. 

We therefore chose to generate using a BAC 

construct that expresses the eGFP gene under 

the control of UCHL1 promoter.

Finally, how important is it for women to be 

fostered in science and technology to help 

drive innovation forward?

I think women have the potential to lead the way 

in innovation because they have a different way 

of leading – with understanding, compassion 

and desire. Innovation stems from our ability 

to see what others do not, and is fuelled by our 

will to make a difference in the world. In my 

opinion, women have an intrinsic ability to be 

innovative and creative. When given an equal 

chance, women always do well and exceed 

any expectations. Thus, in addition to being 

a scientist, I am a keen supporter of women 

in science.

I am one of the Women in STEM faculty 

members and am on the board of the Turkish 

American Women Scholar Fund (TAWSF), 

which funds the college education of young 

women who are accepted to universities but 

have socioeconomic limitations. So far, we have 

helped  over 125 female students to graduate 

and we will continue to offer assistance.

Dr Hande Özdinler

 is a neurobiologist whose research into upper motor neuron biology has 

unearthed many significant findings. She discusses her motivations and vision for her own research 

and that of young women scientists

Highlighting the importance 

of upper motor neurons

INTERNATIONAL INNOVATION

NEUROSCIENCE

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Researchers at the 

Northwestern University Feinberg School of Medicine

, USA, 

have made several important findings in their research on a neurodegenerative 

disorder that renders patients paralysed. In facilitating analysis of specific 

neurons, there is hope of a cure in the future

Hopes for the future of 

neurodegenerative diseases

AMYOTROPHIC LATERAL SCLEROSIS

 (ALS) 

is a disorder that leads to the deterioration 

of neurons in the spinal cord, brainstem and 

brain. As many of these neurons control 

voluntary movement, patients are often 

rendered paralysed by the condition. The 

disorder is known also as Lou Gehrig’s disease, 

named after the former American baseball 

player whose career – and life – was tragically 

cut short as a result of this disease. Currently, 

there is no known cure for the condition, which 

affects two in every 100,000 people.

Attempts to understand the underlying causes 

of neurodegenerative diseases such as ALS 

are challenging for various reasons. Not only is 

the brain one of the most complex organisms 

known to science, it is made up of billions upon 

billions of neurons and non-neuronal cells. 

These vast numbers make it extremely difficult 

to pinpoint the specific neuron populations 

affected by ALS, thereby hindering 

development of effective 

treatment strategies.

Indeed, in addition to the 

thousands of different types of 

neurons and non-neuronal cells, 

ALS is known to only affect some 

neurons and, even then, does not 

affect them to the same degree. 

While some neurons might show 

vulnerability from the outset of 

the disease, others appear to be 

intact. The complexity of the brain 

makes isolating those affected 

neurons from their unaffected 

counterparts particularly difficult, but is a 

necessary step in understanding why they 

become vulnerable and degenerate in patients. 

SPOTLIGHTING SPECIFIC NEURONS

Over the past few years, researchers at the 

Northwestern University Feinberg School 

of Medicine have given cause for hope in 

successfully treating this extremely debilitating 

condition. Led by Dr Hande Özdinler, the 

team has developed innovative approaches to 

studying the biology of motor neurons in the 

brain that become vulnerable as a result of 

ALS. Indeed, Özdinler became the first person 

to label, isolate and culture the corticospinal 

motor neurons (CSMN), in an effort to 

understand their requirements for survival.

CSMN are extremely complex neurons and 

control voluntary motor function. They are 

therefore of particular interest to researchers 

investigating ALS. Özdinler’s research now 

enables direct investigation of CSMN by 

employing novel cellular and molecular 

approaches. “Being able to see the neurons 

that become vulnerable in the disease has 

been very important, because for the first time 

we were able to see and identify them within 

the complex and heterogeneous structure of 

the brain,” explains Özdinler. “This allowed 

their isolation as a pure neuron population and 

determined why they become vulnerable in the 

disease while others remain healthy.”

ENABLING APPLICATION DEVELOPMENT

Finding a means of accessing the information 

directly from the neurons affected by ALS is 

LES TURNER ALS SYMPOSIUMS

Özdinler is organising meetings and 

symposiums to bring people together 

so that new research projects can be 

initiated. To find out more, visit: 

http://bit.ly/fourth_ALS_symposium 

http://bit.ly/fifth_ALS_symposium

www.internationalinnovation.com

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BRINGING LIGHT TO THE UPPER MOTOR NEURONS 

IN AMYOTROPHIC LATERAL SCLEROSIS

OBJECTIVES

•  To further understanding of the causes of 

amyotrophic lateral sclerosis (ALS) through using 

innovative approaches to study corticospinal motor 

neurons (CSMN)

•  To emphasise the crucial role that upper motor 

neurons play in the development of ALS to help find 

a cure

PARTNERS

Cognitive Neurology and Alzheimer’s Disease 

Center, USA

Robert H Lurie Comprehensive Cancer Research 

Center at Northwestern University, USA

FUNDING

Les Turner ALS Foundation

ALS Association

US National Institutes of Health (NIH)

CONTACT

Dr Hande Özdinler

Assistant Professor in Neurology

Feinberg School of Medicine

Northwestern University

303 E Chicago Ave

Chicago

Illinois 60611

USA

T [phone]

E [e-mail] 

http://bit.ly/Ozdinler_profile

http://bit.ly/Ozdinler_lab

@DrOzdinler

http://bit.ly/LI_Ozdinler

HANDE ÖZDINLER

 is trained in 

the fields of molecular biology, 

genetics, cell biology, anatomy and 

neuroscience. Her research focuses 

on CSMN and she is Founding 

Director of the second Les Turner ALS Laboratory at 

Northwestern University, USA.  She received awards 

from Harvard and Northwestern University for her 

ability to study these neuron populations in detail. 

of extreme importance and enables analysis 

of those of specific interest without affecting 

other neurons. Previous research endeavours 

have used cell lines that are not related to the 

disease, or differentiated neurons that are 

forced to become one neuron type, despite 

carrying many different variations. Özdinler’s 

research is exciting because it moves away 

from former practices, uncovering many of the 

mysteries associated with ALS. “We are at the 

doorstep of many important discoveries,” she 

says. “Our research will reveal the mystery 

of why these neurons die, while others 

remain healthy.”

Finding a means to analyse the neurons 

involved in the paralysis associated with ALS 

– without unduly affecting other neurons – is 

crucial to the development of successful 

therapeutic applications. Finding an effective 

treatment for the condition is one thing, but 

unless that treatment can be delivered to the 

cells responsible, any treatment will remain 

ineffective. As their studies continue, so too 

does the impact of their findings, with other 

studies revealing potential detection markers 

for the diseases in which CSMN are affected, 

including hereditary spastic paraplegia, primary 

lateral sclerosis as well as ALS.

PULLING IN THE SAME DIRECTION

Özdinler’s research is funded and supported 

by the US National Institutes of Health (NIH), 

the ALS Association and, most significantly, by 

the Les Turner ALS Foundation, which Özdinler 

readily acknowledges: “Foundations are the 

engines of innovation. They are founded by 

people who want to implement change and have 

the energy and desire to make that happen. 

They generate a momentum that no one can 

resist. If there were no active foundations for 

causes that are important, we would not be able 

to move the field forward at such a speed”.

The ALS Association is the largest in the US, 

and the Les Turner ALS Foundation is one of 

the first foundations in the world to promote 

a better life for patients affected by ALS, and 

encourages and facilitates research into 

understanding the biology of the disease and 

finding an effective cure.

ALS associations and foundations have 

embraced initiatives like the ‘ice bucket 

challenge’ to provide people with a voice to 

communicate their desire to stop the disease. It 

is important that researchers such as Özdinler 

take up the challenge laid before them to make 

a real difference to people’s lives. “Now the ball 

is in our court,” says Özdinler. “We have to be 

as ambitious as the patients and caregivers to 

find a cure. It’s not really about papers, grants 

and promotions – it is about getting together to 

work towards a solution.” 

Özdinler’s research has highlighted the 

important role that upper motor neurons play 

in motor neuron diseases where movement 

is impaired, thereby encouraging other 

researchers around the world to focus their 

energies on these particular neurons to develop 

a cure. Emphasising this importance could 

signal positive change for ALS patients, which 

is certainly something to be celebrated.

FUNDING SUCCESS

To continue research on amyotrophic lateral sclerosis (ALS), Özdinler was awarded 

over US $2.5 million in new grants from the US National Institutes of Health (NIH) and 

the ALS Association – a record amount for a single young investigator to receive at one 

time. Visit: 

http://bit.ly/Ozdinlar_grants

AAV-GFP serotypes

 

and 

red fluorescent 

microspheres

AAV-GFP serotypes

 

and 

red fluorescent 

microspheres

AAV-GFP serotypes

AAV-GFP serotypes

DIRECT CORTICAL INJECTION

CORTICOSPINAL TRACT INJECTION

Red fluorescent 

microspheres

Red fluorescent 

microspheres

INTERNATIONAL INNOVATION

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