Susan Ackerman (neuroscientist)

Last updated
Susan L. Ackerman
Nationality American
Alma mater California State University, Chico, University of California, Los Angeles
Known for UNC5C, Harlequin mice
Scientific career
Fields neuroscience, genetics
Institutions University of California, San Diego, The Jackson Laboratory, Howard Hughes Medical Institute, Massachusetts General Hospital, Tufts University, University of Maine, Orono

Susan L. Ackerman is an American neuroscientist and geneticist. Her work has highlighted some of the genetic and biochemical factors that are involved in the development of the central nervous system and age-related neurodegeneration. [1] Her research is aimed at helping scientists understand what causes several types of neurodegeneration in mammals. This research, and others' like it, may lead to cures for neurodegenerative diseases. Ackerman is a professor at University of California San Diego. She was formerly a professor at the Jackson Laboratory and the Sackler School of Graduate Biomedical Sciences at Tufts University. She also serves as an adjunct professor at the University of Maine, Orono. Ackerman was an associate geneticist at Massachusetts General Hospital in Boston, Massachusetts. [2]

Contents

Education

As an undergraduate, Ackerman attended California State University (Chico), [2] graduating with a Bachelor of Arts degree in Chemistry, and a Bachelor of Arts degree in Biology. [2] Subsequently, Ackerman pursued graduate studies, earning a Doctorate in Biology at the UCLA. [2]

Career and research

Since 2005, Ackerman has served as an investigator at the Howard Hughes Medical Institute. [2] Her work there has centered on the mice that are available through the Jackson Laboratory, known as the Jax mice. [2] These mice have a wide array of genotypic mutations, which lead to different phenotypic expression. Ackerman observes these mice and investigates the genotypic variations that lead to defects in mice. She then investigates the product of these genes and how they affect neurological development and preservation. [2] She was elected a member of the National Academy of Sciences and the American Academy of Arts and Sciences in April 2019. [3]

Unc5c

Ackerman's research has centered largely on the Unc5c gene. [2] The gene product of Unc5c is the Unc5c protein, a neurological netrin receptor. [4] Her research on Unc5c protein revealed that the protein is integral in the development of the corpus callosum, the neurons that form the connection between the two hemispheres of the brain. A mutation in the Unc5c gene, in association with other mutated genes, leads to a degeneration of the corpus callosum. However, if Unc5c is the only gene that is mutated, no noticeable difference in the corpus callosum is present. This is because the Unc5c receptor is only integral in the formation of the corpus callosum in early-born, deep layer neurons. These neurons comprise a small percentage of the corpus callosum relative to the late-born, upper layer neurons. [4]

Harlequin mice

Ackerman's research has also dealt with genetic variations that lead to neurons being more susceptible to oxidative damage. This oxidative damage leads to apoptosis in many neurons. The research centers on the Harlequin mice, who have a proviral insertion in the apoptosis-inducing factor ( AIF ) gene. The AIF protein is, as the research shows, a free radical scavenger, saving cells from and reducing oxidative damage. The proviral insertion into this gene causes an 80% reduction in expression, causing oxidative damage in neurons as they age. [5]

Other research

Other projects Ackerman has been involved in include the mutation of a U2 snRNA and its connection to neurodegeneration, an editing defective tRNA synthetase that leads to protein misfolding and neurodegeneration, and ribosome stalling by tRNA mutations that leads to neurodegeneration. [6] [7] [8]

Related Research Articles

<span class="mw-page-title-main">Charcot–Marie–Tooth disease</span> Neuromuscular disease

Charcot–Marie–Tooth disease (CMT) is a hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of the body. This disease is the most commonly inherited neurological disorder, affecting about one in 2,500 people. It is named after those who classically described it: the Frenchman Jean-Martin Charcot (1825–1893), his pupil Pierre Marie (1853–1940), and the Briton Howard Henry Tooth (1856–1925).

<span class="mw-page-title-main">Molecular lesion</span> Damage to the structure of a biological molecule

A molecular lesion or point lesion is damage to the structure of a biological molecule such as DNA, RNA, or protein. This damage may result in the reduction or absence of normal function, and in rare cases the gain of a new function. Lesions in DNA may consist of breaks or other changes in chemical structure of the helix, ultimately preventing transcription. Meanwhile, lesions in proteins consist of both broken bonds and improper folding of the amino acid chain. While many nucleic acid lesions are general across DNA and RNA, some are specific to one, such as thymine dimers being found exclusively in DNA. Several cellular repair mechanisms exist, ranging from global to specific, in order to prevent lasting damage resulting from lesions.

<span class="mw-page-title-main">L1 (protein)</span> Mammalian protein found in Homo sapiens

L1, also known as L1CAM, is a transmembrane protein member of the L1 protein family, encoded by the L1CAM gene. This protein, of 200 to 220 kDa, is a neuronal cell adhesion molecule with a strong implication in cell migration, adhesion, neurite outgrowth, myelination and neuronal differentiation. It also plays a key role in treatment-resistant cancers due to its function. It was first identified in 1984 by M. Schachner who found the protein in post-mitotic mice neurons.

<span class="mw-page-title-main">Neurodegenerative disease</span> Central nervous system disease

A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, tauopathies, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.

Sticky mouse is a murine possessing a gene mutation in the enzyme alanyl-tRNA synthetase (AARS). The sticky mouse, with this particular mutation, presents a good model in which to investigate mechanisms of neuronal degeneration. Its most immediately obvious symptom is a sticky secretion on the mouse's fur ; however, it is accompanied by lack of muscle control, ataxia, alopecia, loss of Purkinje cells in the cerebellum, and eventually, death.

<span class="mw-page-title-main">SOD1</span> Protein-coding gene in the species Homo sapiens

Superoxide dismutase [Cu-Zn] also known as superoxide dismutase 1 or hSod1 is an enzyme that in humans is encoded by the SOD1 gene, located on chromosome 21. SOD1 is one of three human superoxide dismutases. It is implicated in apoptosis, familial amyotrophic lateral sclerosis and Parkinson's disease.

<span class="mw-page-title-main">PARP1</span> Mammalian protein found in Homo sapiens

Poly [ADP-ribose] polymerase 1 (PARP-1) also known as NAD+ ADP-ribosyltransferase 1 or poly[ADP-ribose] synthase 1 is an enzyme that in humans is encoded by the PARP1 gene. It is the most abundant of the PARP family of enzymes, accounting for 90% of the NAD+ used by the family. PARP1 is mostly present in cell nucleus, but cytosolic fraction of this protein was also reported.

The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear DNA damage can contribute to aging, nuclear DNA is the main subject of this analysis. Nuclear DNA damage can contribute to aging either indirectly or directly.

<span class="mw-page-title-main">Lujan–Fryns syndrome</span> Medical condition

Lujan–Fryns syndrome (LFS) is an X-linked genetic disorder that causes mild to moderate intellectual disability and features described as Marfanoid habitus, referring to a group of physical characteristics similar to those found in Marfan syndrome. These features include a tall, thin stature and long, slender limbs. LFS is also associated with psychopathology and behavioral abnormalities, and it exhibits a number of malformations affecting the brain and heart. The disorder is inherited in an X-linked dominant manner, and is attributed to a missense mutation in the MED12 gene. There is currently no treatment or therapy for the underlying MED12 malfunction, and the exact cause of the disorder remains unclear.

<span class="mw-page-title-main">Neuroferritinopathy</span> Medical condition

Neuroferritinopathy is a genetic neurodegenerative disorder characterized by the accumulation of iron in the basal ganglia, cerebellum, and motor cortex of the human brain. Symptoms, which are extrapyramidal in nature, progress slowly and generally do not become apparent until adulthood. These symptoms include chorea, dystonia, and cognitive deficits which worsen with age.

<span class="mw-page-title-main">SATB2</span> Protein-coding gene in the species Homo sapiens

Special AT-rich sequence-binding protein 2 (SATB2) also known as DNA-binding protein SATB2 is a protein that in humans is encoded by the SATB2 gene. SATB2 is a DNA-binding protein that specifically binds nuclear matrix attachment regions and is involved in transcriptional regulation and chromatin remodeling. SATB2 shows a restricted mode of expression and is expressed in certain cell nuclei. The SATB2 protein is mainly expressed in the epithelial cells of the colon and rectum, followed by the nuclei of neurons in the brain.

<span class="mw-page-title-main">Paul Schimmel</span> American chemist

Paul Reinhard Schimmel is an American biophysical chemist and translational medicine pioneer.

<span class="mw-page-title-main">Fig4</span> Protein-coding gene in the species Homo sapiens

Polyphosphoinositide phosphatase also known as phosphatidylinositol 3,5-bisphosphate 5-phosphatase or SAC domain-containing protein 3 (Sac3) is an enzyme that in humans is encoded by the FIG4 gene. Fig4 is an abbreviation for Factor-Induced Gene.

<span class="mw-page-title-main">Congenital mirror movement disorder</span> Medical condition

Congenital mirror movement disorder(CMM disorder) is a rare genetic neurological disorder which is characterized by mirrored movement, sometimes referred to as associated or synkinetic movement, most often in the upper extremity of the body. These movements are voluntary intentional movements on one, ipsilateral, side of the body that are mirrored simultaneously by involuntary movements on the contralateral side.

<span class="mw-page-title-main">Epigenetics of neurodegenerative diseases</span> Field of study

Neurodegenerative diseases are a heterogeneous group of complex disorders linked by the degeneration of neurons in either the peripheral nervous system or the central nervous system. Their underlying causes are extremely variable and complicated by various genetic and/or environmental factors. These diseases cause progressive deterioration of the neuron resulting in decreased signal transduction and in some cases even neuronal death. Peripheral nervous system diseases may be further categorized by the type of nerve cell affected by the disorder. Effective treatment of these diseases is often prevented by lack of understanding of the underlying molecular and genetic pathology. Epigenetic therapy is being investigated as a method of correcting the expression levels of misregulated genes in neurodegenerative diseases.

Jeffrey L. Price is an American researcher and author in the fields of circadian rhythms and molecular biology. His chronobiology work with Drosophila melanogaster has led to the discoveries of the circadian genes timeless (tim) and doubletime (dbt), and the doubletime regulators spaghetti (SPAG) and bride of doubletime (BDBT).

Susan A. Martinis is an American biochemist. She has co-authored over 57 publications in peer reviewed journals and scientific book chapters. Her expertise is in protein:RNA interactions and aminoacyl tRNA synthetases. As of 2019, she is the Vice Chancellor for Research and Innovation at the University of Illinois at Urbana-Champaign.

There are more than 25 genes known to be associated with amyotrophic lateral sclerosis (ALS) as of June 2018, which collectively account for about 70% of cases of familial ALS (fALS) and 10% of cases of sporadic ALS (sALS). About 5–10% of cases of ALS are directly inherited. Overall, first-degree relatives of an individual with ALS have a 1% risk of developing ALS. ALS has an oligogenic mode of inheritance, meaning that mutations in two or more genes are required to cause disease.

Ted M. Dawson is an American neurologist and neuroscientist. He is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases and Director of the Institute for Cell Engineering at Johns Hopkins University School of Medicine. He has joint appointments in the Department of Neurology, Neuroscience and Department of Pharmacology and Molecular Sciences.

<span class="mw-page-title-main">Animal models of Parkinson's disease</span> Models used in Parkinsons disease research

Animal models of Parkinson's disease are essential in the research field and widely used to study Parkinson's disease. Parkinson's disease is a neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The loss of the dopamine neurons in the brain, results in motor dysfunction, ultimately causing the four cardinal symptoms of PD: tremor, rigidity, postural instability, and bradykinesia. It is the second most prevalent neurodegenerative disease, following Alzheimer's disease. It is estimated that nearly one million people could be living with PD in the United States.

References

  1. ↑ "About Susan L. Ackerman, Ph.D." The Jackson Laboratory. Retrieved September 10, 2015.
  2. 1 2 3 4 5 6 7 8 "Susan L. Ackerman, PhD". HHMI.org. Retrieved 2015-11-19.
  3. ↑ "National Academy of Sciences Elects Members and Foreign Associates; Historic Number of Women Elected to Its Membership - 2019". National Academy of Sciences. April 30, 2019.
  4. 1 2 Srivatsa, Swathi; Parthasarathy, Srinivas; Britanova, Olga; Bormuth, Ingo; Donahoo, Amber-Lee; Ackerman, Susan L.; Richards, Linda J.; Tarabykin, Victor (2014-04-17). "Unc5C and DCC act downstream of Ctip2 and Satb2 and contribute to corpus callosum formation". Nature Communications. 5: 3708. Bibcode:2014NatCo...5.3708S. doi:10.1038/ncomms4708. ISSN   2041-1723. PMC   3997811 . PMID   24739528.
  5. ↑ Klein, Jeffrey A.; Longo-Guess, Chantal M.; Rossmann, Marlies P.; Seburn, Kevin L.; Hurd, Ronald E.; Frankel, Wayne N.; Bronson, Roderick T.; Ackerman, Susan L. (2002-09-26). "The harlequin mouse mutation downregulates apoptosis-inducing factor". Nature. 419 (6905): 367–374. Bibcode:2002Natur.419..367K. doi:10.1038/nature01034. ISSN   0028-0836. PMID   12353028. S2CID   4418288.
  6. ↑ Jia, Yichang; Mu, John C.; Ackerman, Susan L. (2012-01-20). "Mutation of a U2 snRNA gene causes global disruption of alternative splicing and neurodegeneration". Cell. 148 (1–2): 296–308. doi:10.1016/j.cell.2011.11.057. ISSN   1097-4172. PMC   3488875 . PMID   22265417.
  7. ↑ Lee, Jeong Woong; Beebe, Kirk; Nangle, Leslie A.; Jang, Jaeseon; Longo-Guess, Chantal M.; Cook, Susan A.; Davisson, Muriel T.; Sundberg, John P.; Schimmel, Paul (2006-09-07). "Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration". Nature. 443 (7107): 50–55. Bibcode:2006Natur.443...50L. doi:10.1038/nature05096. ISSN   1476-4687. PMID   16906134. S2CID   4395135.
  8. ↑ Ishimura, Ryuta; Nagy, Gabor; Dotu, Ivan; Zhou, Huihao; Yang, Xiang-Lei; Schimmel, Paul; Senju, Satoru; Nishimura, Yasuharu; Chuang, Jeffrey H. (2014-07-25). "RNA function. Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration". Science. 345 (6195): 455–459. doi:10.1126/science.1249749. ISSN   1095-9203. PMC   4281038 . PMID   25061210.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.