Jeremy J. Laukka, Ph.D.
Office: 178 Block Health Sciences Building
2011: Ph.D., Molecular Biology and Genetics, Center for Molecular Medicine and Genetics,
Wayne State University School of Medicine, Detroit, Michigan
2005: M.S., Basic Medical Science, Wayne State University School of Medicine, Detroit, Michigan
2003: B.S., Physiology, Michigan State University, College of Natural Science, East Lansing, Michigan
Teaching Philosophy and Interest:
My teaching philosophy in medical education is centered upon the integrative multidisciplinary approach to basic medical science and clinical medicine. Memorization of facts should be less important than a well-rounded education in fundamental principles, training in methods of investigation, and the acquisition of the scientific mind of habit. The value of understanding the clinical implications of gross anatomy, histology, neuroscience, physiology and pathology stimulates and encourages critical thinking, problem solving and emphasizes the unity of the organ systems and to translate this knowledge to practical medicine.
My experience, leadership and interest primarily involves preclinical instruction.
Seeking opportunities to correlate preclinical coursework with clinical problems in
gross anatomy, histology, neuroscience, neuropathology, physiology all reflect my
professional training and continued interest. Writing multidisciplinary integrative
clinical cases is also an important component of my preclinical instruction. Secondarily,
postgraduate medical education in the field of neurology, neuropathology and the field
of neurosurgery and orthopedic surgery are an important component of my life-long
learning and overarching goals as an educator.
The area of translational research that I study is the use of magnetic resonance imaging (MRI) technologies to understand the progression and disease pathogenesis of inherited leukodystrophies. The most important clinical tools for investigating white matter disorders in living patients are magnetic resonance techniques such as conventional MRI, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) to demonstrate macroscopic structural changes, integrity of the microstructural infrastructure and metabolic activity. Interest in CNS white matter disorders started in the early 19th century with research dominating in the areas of pathology. With the advent of modern neuroimaging modalities we can now complement that which is examined pathologically to further monitor white matter disease progression.
A particular disease that I currently investigate is the X-linked leukodystrophy,
Pelizaeus-Merzbacher disease (PMD), named after two German physicians who first described
its most important clinical features and is a rare condition caused by mutations affecting
the gene for proteolipid protein 1 (PLP1, formerly called PLP), resulting in defective
central nervous system (CNS) myelination (Figure 1).
Pelizaeus-Merzbacher disease usually begins during infancy and signs of the disease may be present at birth or in the first few weeks of life. The first recognizable sign is a form of involuntary movement of the eyes called nystagmus. The nystagmus tends to improve with age. Some infants have stridor (labored and noisy breathing). Infants may show hypotonia (lack of muscle tone; floppiness) at first, but eventually, over several years, develop spasticity (a type of increased muscle tone or stiffness of the muscles and joints). Motor and intellectual milestones are also delayed. The clinical spectrum of PMD is manifested by a very heterogeneous phenotype and can be classified as:
1. Severe or connatal: caused by missense mutations is apparent at birth or in the first few weeks of life. Clinical finding include pendular nystagmus, hypotonia, pharyngeal weakness and stridor. Motor deficits are severe. Hypotonia later evolves into spasticity of the extremities. Verbal expression is limited, although comprehension may be retained. Affected children may die early in infancy or early childhood.
2. Classic form: most common form of PMD and those affected have overexpression of the PLP1 gene (duplication). Affected children have hypotonia, nystagmus, develop titubation (tremor of the head and neck), ataxia and spastic quadriparesis beginning in the first 5 years of life. Ambulation is often less severe with some purposeful voluntary control of the arms, but over time a gradual loss of motor behavior is accompanied by an increase in spasticity.
3. PLP1 null syndrome: relatively mild form and is distinguished by the absence of nystagmus accompanied
by the presence of mild spastic quadriparesis that affects mostly the legs, with ataxia
and demyelinating peripheral neuropathy. Affected patients generally ambulate better
than those with classic PMD, but progress more rapidly due to degenerating axons while
maintaining relatively normal myelin thickness.
The clinical diagnosis generally includes the clinical findings listed above along with a family history consistent with X chromosome transmission. The most useful screening test after the neurologic examination, family history and genetic testing is a conventional MRI of the brain, which is a relatively sensitive test for leukodystrophies. Although conventional MRI scans provide necessary anatomical detail beneficial for detecting abnormalities, limitations also co-exist.
The development of diffusion tensor – magnetic resonance imaging (DTI-MRI), a novel neuroimaging modality allows a greater degree of sensitivity towards characterizing the effects of the neurological disease by probing into the cytoarchitecture of the CNS tissue. Because patients serve as their own baseline reference, DTI makes it possible to follow subjects longitudinally to determine how the microstructural properties changes over time.
In my collaborative research, one of the primary objectives is to investigate using novel MRI modalities more sensitive and specific markers of the pathobiologic effects of the disease and to more robustly monitor disease progression and response to treatment. There is currently no non-invasive modality capable of assessing the axonal and myelin components explicitly. However, a number of MR techniques are available that allow the study of these structures by indirect methods.
Research in the area of PMD is rewarding, due to its intrinsic value in understanding diverse neurologic conditions, but more importantly to show the families of PMD children that the field of translation neuroscience has a great interest in establishing a clinical tool to following the natural history of PMD, and potentially for its application in evaluation in future therapies.
To learn more about PMD, please see the following websites:
Laukka J., Makki M., Stanley J., Lafleur T., Garbern J., Kamholz J. Diffusion Tensor Imaging of Patients with Preoteolipid Protien 1 Gene Mutations. J Neurosci Res. 2014 Dec; 92 (12): 1723-32.
Laukka J. Pelizaeus-Merzbacher Disease: An inherited leukodystrophy. Natural history studies in Understanding neurogenetic disorders. Int J Neurol Neurother, 2014, 1:002e.
Laukka J., Garbern JY, Trepanier A., Hobson G., Gow. A and Kamholz J. Neuroradiologic
correlates of clinical disability and progression in the X-Linked Leukodystrophy Pelizaeus-Merzbacher
Disease. Journal of Neurological Sciences. J. Neurol Sci. 2013 Dec 15;335(1-2):75-81.
Laukka J. Lovell K., Sima A., Skoff R., Kamholz J. Neuropathologic insights into the X-linked leukodystrophy Pelizaeus-Merzbacher disease. J Neuropath Exp Neur 2012. 71:6. 559.
Uhal BD., Rayford H., Zhuang J., Li Xiaopeng. Laukka J., Soledad-Conrad V. Apoptosis-dependent acute lung injury and repair after intratracheal instillation of norepinephrine in rats. Exp Physiol. 2003 Mar;88(2):269-75.
Uhal BD., Wang R., Laukka J., Zhuang J., Soledad-Conrad V., Filippatoa G. Inhibition of amiodarone-induced lung fibrosis but not alveolitis by angiotensin system antagonists. Journal of Pharmacology and Toxicology, in press for Vol 91, Issue 6 (Dec), 2002.
Uhal BD, H. Rayford, X. Li, J. Laukka, J Zhaung and V Conrad. Alveolar epithelial apoptosis and acute lung injury by intratracheal instillation of norepinephrine. Faseb. J. 16:A412, 2002.
Laukka J, Nallapati C, SohiJ, RaziSD, KhatibD, GoradiaD, StanleyJ, Kamholz J.Pelizaeus-Merzbacher disease: a diffusion tensor Imaging study in patients with PLP1 duplications. Am Soc Neuro Radiol (2015).
Rathnam A, Sohi j, Khatib D, Laukka J, Kamholz J, Stanley J. Evidence of altered high-energy phosphate and membrane phospholipid metabolism in Pelizaeus-Merzbacher patients with PLP1 duplications using ³¹P magnetic resonance spectroscopy. Int Soc Mag Reson, (2015).
Malek I Makki and Jeremy J Laukka. Heterogenous PLP1 mutations express differing pathology of the corpus callosum in Pelizaeus-Merzbacher disease. Int Soc Mag Reson, (2015).
Malek I Makki and Jeremy J Laukka. Assessing the level of pathology of the corticospinal pathway in patients with plp1 mutations using diffusiontensor. Int Soc Mag Reson, (2015).
LaFleur T, Kamholz J, Makki M, Trepanier A, Gow A, Fuerst D, Garbern J, Laukka J. Radial diffusion is increased in patients with Pelizaeus-Merzbacher disease. Neurology 2013; 80. (2013).
Laukka J. Pelizaeus-Merzbacher disease: White matter atrophy correlates to clinical disability. Pediatr Radiol 42 Suppl 2: S177-S401 (2012).
Makki M, Laukka J, Garbern J. Microstructural abnormalities in the Corpus Callosum of patients with Pelizaeus-Merzbacher disease with different PLP1 mutations. Proc Int Soc Mag Reson Med, 17, (2012).
Laukka J. Charaterizing the X-Linked Leukodystrophy Pelizaeus-Merzbacher disease using Diffusion Tensor Imaging. Pro Am Soc Neuro Radiol, Seattle (2011).