Bradlee L. Heckmann is an American biologist, pharmacologist. Heckmann holds academic appointments as a
neuroimmunologist at the Byrd Alzheimer's Center and USF Health Neuroscience Institute and is assistant professor in
molecular medicine at the USF Health Morsani College of Medicine. Heckmann's research has been focused on understanding the regulation of inflammatory and metabolic processes in the central nervous system, with particular emphasis on
neurodegenerative
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, mul ...
diseases including
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
and the role of the
autophagy
Autophagy (or autophagocytosis; from the Greek language, Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-depe ...
machinery in this setting.
Education
Heckmann graduated from
Lexington Catholic High School
Lexington Catholic High School is a Roman Catholic high school located in the Rosemill neighborhood in Lexington, Kentucky. It is located in the Roman Catholic Diocese of Lexington. In 2007, it was named a Blue Ribbon School of Excellence.
Histo ...
in
Lexington, Kentucky
Lexington is a Consolidated city-county, consolidated city coterminous with and the county seat of Fayette County, Kentucky, United States. As of the 2020 United States census, 2020 census the city's population was 322,570, making it the List of ...
prior to attending the
University of Kentucky
The University of Kentucky (UK, UKY, or U of K) is a Public University, public Land-grant University, land-grant research university in Lexington, Kentucky, United States. Founded in 1865 by John Bryan Bowman as the Agricultural and Mechanical ...
, where he graduated with a Bachelor of Science in biology. Heckmann went on to complete his doctoral training in Biochemistry & Molecular Biology at the
Mayo Clinic College of Medicine
The Mayo Clinic College of Medicine and Science (MCCMS; formerly known as Mayo Clinic College of Medicine) is a private graduate-only research university based in Rochester, Minnesota, United States. It trains physicians, scientists, and allied ...
. After completing his formal training he joined the laboratory of
Douglas R. Green at St. Jude Children's Research Hospital where he held the John H. Sununu Endowed Fellowship in immunology.
Research
After studying lipid metabolism and components that regulate lipid turnover while at
Mayo Clinic
Mayo Clinic () is a Nonprofit organization, private American Academic health science centre, academic Medical centers in the United States, medical center focused on integrated health care, healthcare, Mayo Clinic College of Medicine and Science ...
, Heckmann switched his research focus to evaluating the role and regulation of non-canonical
autophagy
Autophagy (or autophagocytosis; from the Greek language, Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-depe ...
in the brain. These studies ultimately led to Heckmann &
Green
Green is the color between cyan and yellow on the visible spectrum. It is evoked by light which has a dominant wavelength of roughly 495570 nm. In subtractive color systems, used in painting and color printing, it is created by a com ...
's discovery of a novel form of the
endocytic
Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested materials. E ...
trafficking pathway.
Heckmann and Green showed that a protein known as
LC3 which helps facilitate vesicle trafficking and fusion, most well known for its role in
autophagy
Autophagy (or autophagocytosis; from the Greek language, Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-depe ...
, was attached to endosomes that contained
β-amyloid
Amyloid beta (Aβ, Abeta or beta-amyloid) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor prot ...
,
a known contributor to Alzheimer's Disease establishment and pathology in humans. As such they named the discovery LC3-associated endocytosis (LANDO).
[
] They further found that inhibition of LC3-associated endocytosis in microglial immune cells of the brain resulted in impaired recycling of cell receptors that recognize β-amyloid, leading to dramatic increases in inflammatory activation.
Heckmann and Green were the first to show that loss of the LC3-associated endocytosis pathway in microglia greatly exacerbated the disease pathology of Alzheimer's Disease and that the LANDO pathway is protective against β-amyloid induced neuroinflammation and neurodegeneration, work recently published in ''Cell''
and featured in mainstream media.
The potential for therapeutically targeting LC3-associated endocytosis for the treatment of devastating conditions including Alzheimer's Disease and cancer is of significant promise.
Additional evidence supporting a significant role for LANDO and other non-canonical uses of the autophagy machinery in neurodegeneration and neuroinflammation were recently published by Drs. Heckmann and Green along with other colleagues including Thomas Wileman demonstrating an important role for LANDO and targeting of neuroinflammation as a therapeutic approach to relieving neuronal and behavioral impairment in a novel, age-associated spontaneous model of Alzheimer's Disease in mice, work that has been published in ''Science Advances''.
More recently, the Heckmann Lab has been exploring new roles for the LANDO pathway in regulating cell death processes in neurodegeneration as well as contribution of metabolic mechanisms and mitochondrial regulation to neuroinflammation. Heckmann has also expanded his interests in neuro-oncology and primary brain tumor biology and the role of single membrane LC3-lipidation (CASM) pathways to tumor immunity and tumor microenvironment inflammation.
Recognition and awards
Heckmann has received multiple awards and honors stemming from his work primarily on LC3-associated endocytosis as well as mainstream media coverage. He has been the recipient of honors including a Ruth L. Kirschstein National Research Service Award, an Aegean Young Investigator Award, an LRP award from the National Cancer Institute, and an Excellence in Science Award and nomination for Prize in Neurobiology from the American Association for the Advancement of Science. Dr. Heckmann was recently featured by AZO Network and ''News Medical'' as a "thought leader in medicine".
Work from Heckmann and his laboratory on LANDO and autophagy in Alzheimer's Disease was recently highlighted by Research Features and an associated podcast including potential new therapeutic routes for treating neurodegenerative diseases.
He also has been elected as a member of the Sigma Xi Research Honor Society and is an overseas Fellow of the Royal Society of Medicine.
External links
Byrd Alzheimer's Institute - USF HealthResearch GateORCID
References
{{DEFAULTSORT:Heckmann, Bradlee
Living people
Year of birth missing (living people)
Scientists from Lexington, Kentucky
21st-century American biologists
American immunologists
University of Kentucky alumni