Daniel Djakiew

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Daniel Djakiew
Djakiew.jpg
Professor
Born1956
Occupation(s)Scholar and Scientist

Daniel Djakiew (born 1956 in Newcastle, Australia) is a scholar, researcher, teacher, and tenured full professor in the Department of Biochemistry and Molecular & Cellular Biology, School of Medicine, Georgetown University, Washington DC.

Contents

Research

At University of Newcastle (1978–1983), he conducted research on the evolution of the male reproductive tract as revealed by monotreme mammals. These studies showed that periurethral glands in the male monotreme represent a rudimentary disseminate prostate (prostate evolution in monotreme mammals), [1] and that the monotreme epididymis has many similarities to that of reptiles compared with scrotal mammals (epididymis evolution from reptiles to mammals). [2] [3] [4] After moving to Georgetown University (1983–present) he collaborated with Johns Hopkins University to demonstrate the physiological role of enhanced oxygen availability in the sperm storage region of the epididymis at cooler scrotal temperatures as a prime mover in the evolution of descended testes in mammals. [5]

He was an early adopter of tissue culture technology [6] as subsequently applied to dual chamber culture systems (1985–1991) to investigate polarized secretion in Sertoli cells [7] and prostate cells, [8] especially as they were used to examine paracrine factors in cell-to-cell interactions. [8] [9]

Studies of prostate cancer (1990–2010) examined the expression of the neurotrophins and their receptors [10] [11] (Trk family and p75NTR) in epithelial cells. These studies revealed the role of the p75NTR as a tumor suppressor [12] in prostate epithelial cells and that loss of p75NTR mRNA stability in tumor cells contributes to malignant transformation of normal cells to a cancer phenotype. [13] Moreover, treatment of tumor cells with selective non-steroidal anti-inflammatory drugs (NSAIDs) was shown to induce re-expression of p75NTR in tumor cells and induce apoptotic cell death. [14] [15] [16]

Djakiew received the young investigator of the year award from the Society for the Study of Fertility (Walpole Lecturer) at Oxford University in 1991. He also received the Distinguished Research in Reproductive Biology Award, University of Newcastle, Australia in 1991. He then was a recipient of a Research Career Development Award from the National Institutes of Health from 1993 to 1998. Subsequently, he received the Chaire de Professeur Invite, L’University d’Angers, France (1996–1997), and cited (November 2020) to be one of the World's Top 2% Scientists by Stanford University. [17]

Djakiew has publications in 73 journals, five review publications and eight book chapters. He has supervised 7 Ph.D. students.

Teaching

Teaching activities (1985–present) at Georgetown University include course director of cell biology/histology across multiple modules for 1st and 2nd year medical students as well as specific lectures therein. Additionally, lectures are given to post-graduate students in the Medical School at Georgetown University. Djakiew was also course director and lecturer of cell biology/histology held at the Prince William Campus of George Mason University for the GeorgeSquared program (2010–2023), a collaborative course of post-graduate studies between Georgetown University and George Mason University.

Service

Djakiew was elected to the university wide faculty senate, and has been appointed to serve on a number of departmental, medical school, and university wide committees.

Related Research Articles

<span class="mw-page-title-main">Echidna</span> Family of mammals

Echidnas, sometimes known as spiny anteaters, are quill-covered monotremes belonging to the family Tachyglossidae, living in Australia and New Guinea. The four extant species of echidnas and the platypus are the only living mammals that lay eggs and the only surviving members of the order Monotremata. The diet of some species consists of ants and termites, but they are not closely related to the American true anteaters or to hedgehogs. Their young are called puggles.

<span class="mw-page-title-main">Mammary gland</span> Exocrine gland in humans and other mammals

A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word mamma, "breast". The mammary glands are arranged in organs such as the breasts in primates, the udder in ruminants, and the dugs of other animals. Lactorrhea, the occasional production of milk by the glands, can occur in any mammal, but in most mammals, lactation, the production of enough milk for nursing, occurs only in phenotypic females who have gestated in recent months or years. It is directed by hormonal guidance from sex steroids. In a few mammalian species, male lactation can occur. With humans, male lactation can occur only under specific circumstances.

<span class="mw-page-title-main">Germ cell</span> Gamete-producing cell

A germ cell is any cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they undergo meiosis, followed by cellular differentiation into mature gametes, either eggs or sperm. Unlike animals, plants do not have germ cells designated in early development. Instead, germ cells can arise from somatic cells in the adult, such as the floral meristem of flowering plants.

<span class="mw-page-title-main">Paracrine signaling</span> Form of localized cell signaling

In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance, as opposed to cell signaling by endocrine factors, hormones which travel considerably longer distances via the circulatory system; juxtacrine interactions; and autocrine signaling. Cells that produce paracrine factors secrete them into the immediate extracellular environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain.

<span class="mw-page-title-main">Neurotrophin</span> Family of proteins

Neurotrophins are a family of proteins that induce the survival, development, and function of neurons.

<span class="mw-page-title-main">Short-beaked echidna</span> Spiny furred egg-laying mammal from Australia

The short-beaked echidna, also known as the short-nosed echidna, is one of four living species of echidna and the only member of the genus Tachyglossus.

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

Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was one of the first to be described. Since it was first isolated by Nobel Laureates Rita Levi-Montalcini and Stanley Cohen in 1956, numerous biological processes involving NGF have been identified, two of them being the survival of pancreatic beta cells and the regulation of the immune system.

<span class="mw-page-title-main">TRPV6</span> Protein-coding gene in the species Homo sapiens

TRPV6 is a membrane calcium (Ca2+) channel protein which is particularly involved in the first step in Ca2+absorption in the intestine.

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

Tropomyosin receptor kinase A (TrkA), also known as high affinity nerve growth factor receptor, neurotrophic tyrosine kinase receptor type 1, or TRK1-transforming tyrosine kinase protein is a protein that in humans is encoded by the NTRK1 gene.

<span class="mw-page-title-main">Low-affinity nerve growth factor receptor</span> Human protein-coding gene

The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic factor receptor. Neurotrophic factor receptors bind Neurotrophins including Nerve growth factor, Neurotrophin-3, Brain-derived neurotrophic factor, and Neurotrophin-4. All neurotrophins bind to p75NTR. This also includes the immature pro-neurotrophin forms. Neurotrophic factor receptors, including p75NTR, are responsible for ensuring a proper density to target ratio of developing neurons, refining broader maps in development into precise connections. p75NTR is involved in pathways that promote neuronal survival and neuronal death.

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

Tropomyosin receptor kinase C (TrkC), also known as NT-3 growth factor receptor, neurotrophic tyrosine kinase receptor type 3, or TrkC tyrosine kinase is a protein that in humans is encoded by the NTRK3 gene.

<span class="mw-page-title-main">Mothers against decapentaplegic homolog 3</span> Protein-coding gene in humans

Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene.

<span class="mw-page-title-main">Transforming protein RhoA</span> Protein and coding gene in humans

Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the RHOA gene. While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility. It acts upon several effectors. Among them, ROCK1 and DIAPH1 are the best described. RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billion years. As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation.

Trk receptors are a family of tyrosine kinases that regulates synaptic strength and plasticity in the mammalian nervous system. Trk receptors affect neuronal survival and differentiation through several signaling cascades. However, the activation of these receptors also has significant effects on functional properties of neurons.

<span class="mw-page-title-main">FGF9</span> Protein-coding gene in the species Homo sapiens

Glia-activating factor is a protein that in humans is encoded by the FGF9 gene.

<span class="mw-page-title-main">Monotreme</span> Order of egg-laying mammals

Monotremes are mammals of the order Monotremata. They are the only known group of living mammals that lay eggs, rather than bearing live young. The extant monotreme species are the platypus and the four species of echidnas. Monotremes are typified by structural differences in their brains, jaws, digestive tract, reproductive tract, and other body parts, compared to the more common mammalian types. Although they are different from almost all mammals in that they lay eggs, like all mammals, the female monotremes nurse their young with milk.

In cellular biology, dependence receptors are proteins that mediate programmed cell death by monitoring the absence of certain trophic factors that otherwise serve as ligands (interactors) for the dependence receptors. A trophic ligand is a molecule whose protein binding stimulates cell growth, differentiation, and/or survival. Cells depend for their survival on stimulation that is mediated by various receptors and sensors, and integrated via signaling within the cell and between cells. The withdrawal of such trophic support leads to a form of cellular suicide.

Mammals are the only animals in which the testes descend from their point of origin into a scrotum. Concurrently, mammals are the only class of vertebrates to evolve a prostate gland starting with prostate evolution in monotreme mammals.

The monotremes represent the order of extant mammals most distantly related to humans. The platypus is indigenous to eastern Australia; the short-beaked echidna is indigenous to Australia and Papua New Guinea; whereas the long-beaked echidna is restricted to Papua New Guinea and Irian Jaya. Since monotremes exhibit characteristics common with both reptiles and therian mammals, they are of great interest for the study of mammalian evolution.

The epididymis, which is a tube that connects a testicle to a vas deferens in the male reproductive system, evolved by retention of the mesonephric duct during regression and replacement of the mesonephros with the metanephric kidney. Similarly, during embryological involution of the paired mesonephric kidneys, each mesonephric duct is retained to become the epididymis, vas deferens, seminal vesicle and ejaculatory duct. In reptiles and birds both the testes and excurrent ducts occur in an intra-abdominal location (testicond). Primitive mammals, such as the monotremes (prototheria), also are testicond. Marsupial (metatheria) and placental (eutheria) mammals exhibit differing degrees of testicular descent into an extra-abdominal scrotum. In scrotal mammals the epididymis is attached to the testes in an extra-abdominal position where the cauda epididymis extends beyond the lowest extremity of the testis. Hence, the cauda epididymis is exposed to the coolest of temperatures compared to all other reproductive structures.

References

  1. Djakiew, D. (1978). Studies of the Male Reproductive Tract of the Echidna (Tachyglossus aculeatus) with particular emphasis on the Epididymis. Honors Thesis, University of Newcastle, Australia.
  2. Djakiew, D. & Jones R.C. (1981). Structural differentiation of the male genital ducts of the echidna (Tachyglossus aculeatus). Journal of Anatomy 132: 187-202.
  3. Djakiew, D. & Jones, J.C. (1983). Sperm maturation, fluid transport, and secretion and absorption of protein in the epididymis of the echidna, Tachglossus aculeatus. Journal of Reproduction and Fertility 68: 445-456.
  4. Djakiew, D. & Jones, R.C. (1982). Stereological analysis of the epididymis of the echidna (Tachyglossus aculeatus) and wistar rat. Australian Journal of Zoology 30: 865-875.
  5. Djakiew, D. & Cardullo, R. (1986). Lower temperature of the cauda epididymidis facilitates the storage of sperm by enhancing oxygen availability. Gamete Research 15: 237-245.
  6. Djakiew, D., Byers, S.W. & Dym, M. (1984). Receptor-mediated endocytosis of transferrin and alpha2-macroglobulin by rat epididymal epithelial cells in vitro. Biology of Reproduction 31: 1073-1085.
  7. Djakiew, D. & Onoda, M. (1993). Multichamber Cell Culture and Directional Secretion. In "The Sertoli Cell", Eds L. Russell & M. Griswold. Cache River Press, Clearwater, Florida, p181-194.
  8. 1 2 Djakiew, D. & Dym, M. (1988). Pachytene spermatocyte proteins influence Sertoli cell function. Biology of Reproduction 39: 1193-1205.
  9. Djakiew, D., Pflug, B.R., Delsite, R., Onoda, M., Lynch, J.H., Arand, G. & Thompson, E.W. (1993). Chemotaxis and chemokinesis of human prostate tumor cell lines in response to human prostate stromal cell secretory proteins containing a specific nerve growth factor-like protein. Cancer Research 53: 1416-1420.
  10. Dalal, R. & Djakiew, D. (1997). Molecular Characterization of neurotrophin expression and the corresponding tropomyosin receptor kinases (trks) in epithelial cells and stromal cells of the human prostate. Molecular and Cellular Endocrinology 134: 15-22.
  11. Pflug, B. & Djakiew, D. (1998). Expression of p75NTR in a human prostate epithelial tumor cell line reduces NGF induced cell growth by activation of programmed cell death. Molecular Carcinogenesis 23: 106-114.
  12. Krygier, S. & Djakiew, D. (2001). The Neurotrophin Receptor p75NTR is a tumor suppressor in the human prostate. Anticancer Research 21: 3749-3756.
  13. Krygier, S. & Djakiew, D. (2001). Molecular characterization of p75NTR loss of the expression in human prostate tumor cells. Molecular Carcinogenesis 31: 46-55.
  14. Quann E., Khwaja, F., Zavitz, K.H. & Djakiew, D. (2007). The Aryl Propionic Acid R-Flurbiprofen Selectively Induces p75NTR-Dependent Decreased Survival of Prostate Tumor Cells. Cancer Research 67: 3254-62.
  15. Quann, E., Khwaja, F., & Djakiew, D. (2007). The p38 MAPK Pathway Mediates Aryl Propionic Acid-Induced messenger RNA Stability of p75NTR in Prostate Cancer Cells. Cancer Research 67: 11402-11410
  16. El Touny, L., Henderson, F., Djakiew, D. (2010). Biochanin A Reduces Drug-Induced p75NTR expression and Enhances Cell Survival: a New in Vitro Assay for Screening Inhibitors of p75NTR Expression. Rejuvenation Research 13(5): 527-537.
  17. Baas, J., Boyack, K., Ioannidis, J. (2020). Data for "Updated science-wide author databases of standardized citation indicators", Mendeley Data, V2, doi: 10.17632/btchxktzyw.2