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The Kroemer Lab is interested in the molecular mechanisms of cellular stress and death. The mode of cellular stress and death that is evoked during cancer treatment has profound therapeutic implications. A systematic search has been launched to identify molecular switches that “decide” which particular cell stress or cell death subroutine is preferentially executed. In addition, cancer cell death modalities and their impact on the immune system are analyzed in a systematic fashion to develop strategies that improve the chances of therapeutic success.

The Cell Biology platform (pictured, right) within the Kroemer Lab is used as a hub to conduct screening approaches as it offers fully automated cell biology workflows that allow for the phenotypic screening of large-scale compound and siRNA libraries. They use a battery of fluorescent biosensor cells to assess all types of cellular stress and death.

To enable this cutting-edge research, the group needed a high-content analysis system that they could fully integrate into an automated platform which also includes compound management and automated cell culture.

Ergonovine or ergonovinine was isolated from the aerial parts of endophyte (Neotyphodium gansuense) infected (E+) drunken horse grass (Achnatherum inebrians), neither of which existed in endophyte-free (E−) plants. Both of these ergot alkaloids had a cytotoxic effect on animal smooth muscle cells and increased cell growth inhibition with greater concentrations, in a significantly (P < 0.05) positive correlation. The median inhibitory concentrations (IC50) for ergonovine and ergonovinine were 71.95 and 72.75 μg/mL, respectively. These results indicate that endophytic ergot alkaloids may be the cause of drunken horse grass poisoning.

Menopause in women occurs at mid-life. Chimpanzees, in contrast, continue to display cycles of menstrual bleeding and genital swelling, suggestive of ovulation, until near their maximum life span of about 60 years. Because ovulation was not confirmed hormonally, however, the age at which chimpanzees experience menopause has remained uncertain. In the present study, we provide hormonal data from urine samples collected from 30 female chimpanzees, of which 9 were old (>30 years), including 2 above the age of 50 years. Eight old chimpanzees showed clear endocrine evidence of ovulation, as well as cycles of genital swelling that correlated closely with measured endocrine changes. Endocrine evidence thus confirms prior observations (cyclic anogenital swelling) that menopause is a late-life event in the chimpanzee. We also unexpectedly discovered an idiopathic anovulation in some young and middle-aged chimpanzees; this merits further study. Because our results on old chimpanzees validate the use of anogenital swelling as a surrogate index of ovulation, we were able to combine data on swelling and urinary hormones to provide the first estimates of age-specific rates of menopause in chimpanzees. We conclude that menopause occurs near 50 years of age in chimpanzees as it does in women. Our finding identifies a basic difference between the human and chimpanzee aging processes: female chimpanzees can remain reproductively viable for a greater proportion of their life span than women. Thus, while menopause marks the end of the chimpanzee’s life span, women may thrive for decades more.