Research Topics

Drug Discovery, Endocrinology, Protein-Nucleic Acid Interactions, Receptor Biochemistry, Regulation of Gene Expression, Signal Transduction

Disease Research Interests

Cancer, Drug Discovery, Neurological and Behavioral Disorders, Trauma, Bleeding & Tissue Regeneration

B.S. 1967 Brooklyn College
Ph.D. 1972 Purdue University
Postdoc. 1972-1973 Stanford University Medical School, 1973-1974 Stanford University
1985 - 1986 Guggenheim Fellow, Center for Cancer Research MIT

Identification and use of small molecule biomodulators as novel anticancer drugs and probes for new regulatory pathways

ErSO, a novel small molecule biomodulator uses a recently unveiled pathway to eradicate advanced breast cancer

More than 90% of deaths due to cancer are due to metastases, or spread, of the cancer. Nearly all metastatic cancers are incurable. Metastatic estrogen receptor a (ERa) positive breast and ovarian cancer are presently incurable and most patients die within a few years. Therefore, our goal is to use our expertise in high throughput screening, cell line development, endocrinology and animal models to identify new pathways in cancer and small molecules that target them.

From a program with Chemistry Professor, Paul Hergenrother, we identified a novel small molecule that acts through ERa to kill breast cancer cells and often induces complete regression without recurrence of large, therapy-resistant primary breast tumors and of lung, bone, and liver metastases and near complete regression of highly lethal brain metastases. Although, complete regression with no recurrence over 4-6 months without treatment was common, tumors that did recur remained fully sensitive to ErSO re-treatment; in >150 mice, we have never seen an ErSO-resistant tumor. ErSO’s unprecedented activity against advanced primary and metastatic ERα-positive breast cancers is achieved by exploiting our finding that estrogen-ERa activates an extranuclear tumor-protective, signaling pathway, termed the anticipatory unfolded protein response (a-UPR). We repurposed this tumor protective pathway by targeting it with ErSO. ErSO kills cancer cells by acting non-competitively through ERa to induce lethal hyperactivation of the anticipatory UPR (a-UPR), triggering rapid necrotic cell death. This game-changing turn-on strategy contrasts with widely used inhibition strategies.

A new essential action of hormones: Anticipatory activation of the Unfolded Protein Response (a-UPR)

The endoplasmic reticulum (EnR) stress sensor, the unfolded protein response, was known as a pathway that reacts to diverse forms of stress by activating signaling pathways that reduce protein production and increase protein-folding capacity. We, and others, identified an alternative type of UPR pathway in which mitogenic hormones, such as estrogen and epidermal growth factor (EGF), act through their receptors to preactivate the UPR in anticipation of future needs for increased protein folding and transport. Our bioinfomatic analysis of tumor data showed that elevated expression of a UPR gene signature at diagnosis is a powerful prognostic marker tightly correlated with subsequent breast cancer recurrence, therapy resistance and poor survival. This recently unveiled pathway of hormone action is conserved from insects to humans and between steroid hormones and peptide hormones.

Representative Recent Awards and Media Coverage

2016 – Present Eugene Howe Scholar in Biochemistry

08/2021 Scripps TV interview (60 stations) “Researchers develop breakthrough compound that kills breast cancer in animals”

08/2021 Nature Reviews Drug Discovery: “UPR activator eliminates breast tumours”

07/2021 Fierce Biotech: “Bayer’s drug that turns a cancer-protective pathway toxic eradicates breast tumors in mice”

07/2021 Medical News Today: “Drug rapidly shrinks metastatic breast cancers in mice”

07/2021 inews.co.UK: “New breast cancer drug shrinks tumours by 99% in three days in mice”

07/2021 BioTech Scope: “New ‘turn-on’ anticancer strategy eradicates breast cancer in days”

Department of Biochemistry
419 Roger Adams Lab.
University of Illinois
600 S. Mathews Avenue
Urbana, IL 61801