Richard A. Lockshin, Ph.D.
Our laboratory has focused for many years on cell death, a field
that now boasts over 100,000 publications and is known also by the
terms "apoptosis" and "programmed cell death". First recognized in
development (where does the tail of a metamorphosing tadpole go?),
cell death is now considered to be a major component of
development, homeostasis, aging, and many diseases. Some examples
- Most developmental abnormalities (teratologies) arise from
excessive or insufficient cell death.
- In the developing central nervous system, as many as half of
the newly-born cells die, with this death being essential for
proper neural development.
- Many forms of cancer are failures of cells to die at the right
- At least half of the cells that die in a heart attack could be
salvaged if we knew how to control cell death.
- A major approach in treating AIDS is to limit the death of the
T-cells (most of which are not infected with virus but rather are
induced to commit suicide), and
- Alzheimer's Disease is inherently a problem of cell death.
We have looked for many years at signaling mechanisms inducing
cells to die as well as the proteases that take the cells apart and
may be the killing mechanism. Currently we focus on two major
directions: Proteases other than caspases (proteases with very
restricted substrate specificity that are the major proteases in
apoptosis) and the acquisition by an embryo of the ability to
undergo apoptosis. These studies have taken us, including many
students, to many countries including (2000-2002) Canada, Spain,
Italy, Sweden, Switzerland, Israel, Austria, and Australia.
When Cells Die, 2nd Edition, ed. By Richard A. Lockshin and
Zahra Zakeri, Wiley Press, New York, 2002 in process.
Mechanisms of Cell Death II. Ann. N.Y. Acad. Sci., ed. by Zahra
Zakeri, Richard A. Lockshin, and Carlos Martinez-A., Preface by R.
A. Lockshin, December 2000, 238 pp.
Mechanisms of Cell Death, Ann. N.Y. Acad. Sci., ed. by Zahra
Zakeri, Richard A. Lockshin, and Luis Benitez-Bribiesca, 1999 213
pp. Preface by R A Lockshin, pp ix-x.
Lockshin RA, Zakeri Z, and Tilly JL, Why Cells Die A
Comprehensive Evaluation of Apoptosis and Programmed Cell Death,
Wiley-Liss, New York, 1998, 680 pp
In press: Zakeri Z and Lockshin RA, Apoptosis in Development. J.
Immunol. Methods. 2001
Lockshin RA and Zakeri Z, 2001. Programmed cell death and
apoptosis: Origins of the theory. Nature Revs. Molec. Cell Biol. 2:
Mammone T, Gan D, Collins D, Lockshin RA, Marenus K, Maes D,
2000, Successful separation of apoptosis and necrosis pathways in
HaCaT keratinocyte cells induced by UVB irradiation, Cell Biol
Lockshin, R.A., 1999, Gender differences: The perspective from
biology. Lupus, 8: 361-364.
Mammone T (PhD SJU), Marenus K, Maes D, Lockshin RA, 1998, The
induction of terminal differentiation markers by the cAMP pathway
in human HaCaT keratinocytes. Skin Pharmacol Appl Skin Physiol 1998
Jochova J, Quaglino D, Zakeri Z, Woo K, Sikorska M, Weaver V,
and Lockshin RA (1997) Protein synthesis, DNA degradation, and
morphological changes during programmed cell death in labial glands
of Manduca sexta. Developmental Genetics 21: 249-257.
Jochova, J., Zakeri, Z., and Lockshin, R. A., 1997, Early
collapse of the cytoskeleton in the programmed cell death of the
Drosophila salivary gland , Cell Death and Differentiation 4: